bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Diverse Alphacoronaviruses and Genomic Characterization of a Novel Severe Acute Respiratory Syndrome-Like Coronavirus from Bats in China
Authors: He Biao , Zhang Yuzhen , Xu Lin , Yang Weihong , Yang Fanli , Feng Yun , Xia Lele , Zhou Jihua , Zhen Weibin , Feng Ye , Guo Huancheng , Zhang Hailin , Tu Changchun 
Published: April 2014

ABSTRACT
Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been identified in bats in China, Europe, and Africa, most have a genetic organization significantly distinct from human/civet SARS CoVs in the receptor-binding domain (RBD), which mediates receptor binding and determines the host spectrum, resulting in their failure to cause human infections and making them unlikely progenitors of human/civet SARS CoVs. Here, a viral metagenomic analysis of 268 bat rectal swabs collected from four counties in Yunnan Province has identified hundreds of sequences relating to alpha- and betacoronaviruses. Phylogenetic analysis based on a conserved region of the RNA-dependent RNA polymerase gene revealed that alphacoronaviruses had diversities with some obvious differences from those reported previously. Full genomic analysis of a new SARS-like CoV from Baoshan (LYRa11) showed that it was 29,805 nucleotides (nt) in length with 13 open reading frames (ORFs), sharing 91% nucleotide identity with human/civet SARS CoVs and the most recently reported SARS-like CoV Rs3367, while sharing 89% with other bat SARS-like CoVs. Notably, it showed the highest sequence identity with the S gene of SARS CoVs and Rs3367, especially in the RBD region. Antigenic analysis showed that the S1 domain of LYRa11 could be efficiently recognized by SARS-convalescent human serum, indicating that LYRa11 is a novel virus antigenically close to SARS CoV. Recombination analyses indicate that LYRa11 is likely a recombinant descended from parental lineages that had evolved into a number of bat SARS-like CoVs.

IMPORTANCE
Although many severe acute respiratory syndrome-like coronaviruses (SARS-like CoVs) have been discovered in bats worldwide, there are significant different genic structures, particularly in the S1 domain, which are responsible for host tropism determination, between bat SARS-like CoVs and human SARS CoVs, indicating that most reported bat SARS-like CoVs are not the progenitors of human SARS CoV. We have identified diverse alphacoronaviruses and a close relative (LYRa11) to SARS CoV in bats collected in Yunnan, China. Further analysis showed that alpha- and betacoronaviruses have different circulation and transmission dynamics in bat populations. Notably, full genomic sequencing and antigenic study demonstrated that LYRa11 is phylogenetically and antigenically closely related to SARS CoV. Recombination analyses indicate that LYRa11 is a recombinant from certain bat SARS-like CoVs circulating in Yunnan Province.
Interferon Regulatory Factor 1 Restricts Gammaherpesvirus Replication in Primary Immune Cells
Authors: Mboko Wadzanai P. , Mounce Bryan C. , Emmer Joseph , Darrah Eric , Patel Shailendra B. , Tarakanova Vera L. 
Published: April 2014

ABSTRACT
Gammaherpesviruses are ubiquitous pathogens that establish a lifelong infection and are associated with cancer. In spite of the high seroprevalence of infection, the risk factors that predispose the host toward gammaherpesvirus-induced malignancies are still poorly understood. Interferon (IFN) regulatory factor 1 (IRF-1) is a tumor suppressor that is also involved in the regulation of innate and adaptive immune responses. On the basis of its biology, IRF-1 represents a plausible host factor to attenuate gammaherpesvirus infection and tumorigenesis. In this study, we show that IRF-1 restricts gammaherpesvirus replication in primary macrophages, a physiologically relevant immune cell type. In spite of the known role of IRF-1 in stimulating type I IFN expression, induction of a global type I IFN response was similar in IRF-1-deficient and -proficient macrophages during gammaherpesvirus infection. However, IRF-1 was required for optimal expression of cholesterol-25-hydroxylase, a host enzyme that restricted gammaherpesvirus replication in primary macrophages and contributed to the antiviral effects of IRF-1. In summary, the current study provides an insight into the mechanism by which IRF-1 attenuates gammaherpesvirus replication in primary immune cells, a mechanism that is likely to contribute to the antiviral effects of IRF-1 in other virus systems.

IMPORTANCE
Interferon regulatory factor 1 (IRF-1) is a transcription factor that regulates innate and adaptive immune responses and functions as a tumor suppressor. IRF-1 restricts the replication of diverse viruses; however, the mechanisms responsible for the antiviral effects of IRF-1 are still poorly understood. Gammaherpesviruses are ubiquitous pathogens that are associated with the induction of several malignancies. Here we show that IRF-1 expression attenuates gammaherpesvirus replication in primary macrophages, in part by increasing expression of cholesterol-25-hydroxylase (CH25H). CH25H and its product, 25-hydroxycholesterol, restrict replication of diverse virus families. Thus, our findings offer an insight into the mechanism by which IRF-1 attenuates the replication of gammaherpesviruses, a mechanism that is likely to be applicable to other virus systems.
N-Myc Interactor Inhibits Prototype Foamy Virus by Sequestering Viral Tas Protein in the Cytoplasm
Authors: Hu Xiaomei , Yang Wei , Liu Ruikang , Geng Yunqi , Qiao Wentao , Tan Juan 
Published: April 2014

ABSTRACT
Foamy viruses (FVs) are complex retroviruses that establish lifelong persistent infection without evident pathology. However, the roles of cellular factors in FV latency are poorly understood. This study revealed that N-Myc interactor (Nmi) could inhibit the replication of prototype foamy virus (PFV). Overexpression of Nmi reduced PFV replication, whereas its depletion by small interfering RNA increased PFV replication. The Nmi-mediated impairment of PFV replication resulted from the diminished transactivation by PFV Tas of the viral long terminal repeat (LTR) and an internal promoter (IP). Nmi was determined to interact with Tas and abrogate its function by sequestration in the cytoplasm. In addition, human and bovine Nmi proteins were found to inhibit the replication of bovine foamy virus (BFV) and PFV. Together, these results indicate that Nmi inhibits both human and bovine FVs by interfering with the transactivation function of Tas and may have a role in the host defense against FV infection.

IMPORTANCE
From this study, we report that the N-Myc interactor (Nmi), an interferon-induced protein, can interact with the regulatory protein Tas of the prototype foamy virus and sequester it in the cytoplasm. The results of this study suggest that Nmi plays an important role in maintaining foamy virus latency and may reveal a new pathway in the interferon-mediated antiviral barrier against viruses. These findings are important for understanding virus-host relationships not only with FVs but potentially for other retroviruses as well.
Association of Satellites with a Mastrevirus in Natural Infection: Complexity of Wheat Dwarf India Virus Disease
Authors: Kumar Jitendra , Kumar Jitesh , Singh Sudhir P. , Tuli Rakesh 
Published: April 2014

ABSTRACT

In contrast to begomoviruses, mastreviruses have not previously been shown to interact with satellites. This study reports the first identification of the association of satellites with a mastrevirus in field-grown plants. Two alphasatellite species were detected in different field samples of wheat infected with
Wheat Dwarf India Virus
(WDIV), a Cotton leaf curl Multan alphasatellite (CLCuMA) and a Guar leaf curl alphasatellite (GLCuA). In addition to the alphasatellites, a betasatellite, Ageratum yellow leaf curl betasatellite (AYLCB), was also identified in the wheat samples. No begomovirus was detected in the wheat samples, thus establishing association of the above-named satellites with WDIV. Agrobacterium-mediated inoculation of WDIV in wheat, in the presence of either of the alphasatellites or the betasatellite, resulted in infections inducing more severe symptoms. WDIV efficiently maintained each of the alphasatellites and the betasatellite in wheat. The satellites enhanced the level of WDIV DNA in wheat. Inoculation of the satellites isolated from wheat with various begomoviruses into
Nicotiana tabacum
demonstrated that these remain capable of interacting with the viruses with which they were first identified. Virus-specific small RNAs accumulated in wheat upon infection with WDIV but were lower in abundance in plants coinfected with the satellites, suggesting that both the alphasatellites and the betasatellite suppress RNA silencing. These results suggest that the selective advantage for the maintenance of the alphasatellites and the betasatellite by WDIV in the field is in overcoming RNA silencing-mediated host defense.

IMPORTANCE
Wheat is the most widely cultivated cereal crop in the world. A number of viruses are important pathogens of wheat, including the viruses of the genus
Mastrevirus
, family
Geminiviridae
. This study reports the association of subgenomic components, called satellites (alpha- and betasatellites), with a mastrevirus,
Wheat Dwarf India Virus
(WDIV), isolated from two distant locations in India. This study reports the first identification of the satellites in a monocot plant. The satellites enhanced accumulation of WDIV and severity of disease symptoms. The satellites lowered the concentration of virus-specific small RNAs in wheat plants, indicating their silencing suppressor activity. The involvement of the satellites in symptom severity of the mastrevirus can have implications in the form of economic impact of the virus on crop yield. Understanding the role of the satellites in disease severity is important for developing disease management strategies.
Outer Membrane Protein OmpW Is the Receptor for Typing Phage VP5 in the Vibrio cholerae O1 El Tor Biotype
Authors: Xu Donglei , Zhang Jingyun , Liu Jie , Xu Jialiang , Zhou Haijian , Zhang Lijuan , Zhu Jun , Kan Biao 
Published: April 2014

ABSTRACT

Phage typing is used for the subtyping of clones of epidemic bacteria. In this study, we identified the outer membrane protein OmpW as the receptor for phage VP5, one of the typing phages for the
Vibrio cholerae
O1 El Tor biotype. A characteristic 11-bp deletion in
ompW
was observed in all epidemic strains resistant to VP5, suggesting that this mutation event can be used as a tracing marker in cholera surveillance.
The effect of weekly text-message communication on treatment completion among patients with latent tuberculosis infection: study protocol for a randomised controlled trial (WelTel LTBI)
Authors: van der Kop Mia L , Memetovic Jasmina , Patel Anik , Marra Fawziah , Sadatsafavi Mohsen , Hajek Jan , Smillie Kirsten , Thabane Lehana , Taylor Darlene , Johnston James , Lester Richard T 
Published: April 2014

IntroductionInterventions to improve adherence to treatment for latent tuberculosis infection (LTBI) are necessary to improve treatment completion rates and optimise tuberculosis (TB) control efforts. The high prevalence of cell phone use presents opportunities to develop innovative ways to engage patients in care. A randomised controlled trial (RCT), WelTel Kenya1, demonstrated that weekly text messages improved antiretroviral adherence and clinical outcomes among patients initiating HIV treatment. The aim of this study is to determine whether the WelTel intervention can improve treatment completion among patients with LTBI and to evaluate the intervention's cost-effectiveness.Methods and analysisThis open, two-site, parallel RCT (WelTel LTBI) will be conducted at TB clinics in Vancouver and New Westminster, British Columbia, Canada. Over 2 years, we aim to recruit 350 individuals initiating a 9-month isoniazid regimen. Participants will be randomly allocated to an intervention or control (standard care) arm in a 1:1 ratio. Intervention arm participants will receive a weekly text-message ‘check-in’ to which they will be asked to respond within 48 h. A TB clinician will follow-up instances of non-response and problems that are identified. Participants will be followed until treatment completion (up to 12 months) or discontinuation. The primary outcome is self-reported treatment completion (taking ≥80% of doses within 12 months). Secondary outcomes include daily adherence (percentage of days participants used medication as prescribed) and time to treatment completion. Patient satisfaction with the intervention will be evaluated, and the intervention's cost-effectiveness will be analysed through decision-analytic modelling.Ethics and disseminationEthical approval has been obtained from the University of British Columbia. This trial will test the efficacy and cost-effectiveness of the WelTel intervention to improve treatment completion among patients with LTBI. Trial results and economic evaluation will help inform policy and practice on the use of WelTel in this population.Trial registration numberClinicalTrials.govNCT01549457.
Characterization of gas flow through low-permeability claystone: laboratory experiments and two-phase flow analyses
Authors: Senger Rainer , Romero Enrique , Ferrari Alessio , Marschall Paul 
Published: April 2014

Abstract
For the characterization of gas migration through a low-permeability clay host rock for deep underground repositories, a comprehensive understanding of the relevant phenomena of gas and fluid flow through low-permeability clay is required. The National Cooperative for the Disposal of Radioactive Waste (Nagra) in Switzerland has developed a comprehensive programme to characterize gas flow in low-permeability Opalinus Clay through laboratory tests and detailed numerical analyses for developing appropriate constitutive models.

Laboratory tests were performed on cores by two different laboratories, the Laboratory for Soil Mechanics at EPFL and the Department of Geotechnical Engineering and Geosciences at UPC. Loading tests were performed by both laboratories to study rock compressibility at different stress levels and water permeability dependence on void ratio. The water retention behaviour demonstrated by EPFL and UPC produced comparable results. Water permeability tests and fast controlled-volume air injection experiments were performed in a triaxial cell under isotropic stress conditions on two samples with flow parallel and normal to the bedding planes. A confining stress of 15 MPa was applied during gas testing, corresponding to a lithostatic pressure at a depth of
c.
600 m below ground.

For detailed analyses, the two-phase flow code TOUGH2 (

Pruess
et al.
1999

) was used. This considers fluid flow in both liquid and gas phases under the influence of pressure, viscous and gravity forces, according to Darcy's law. The standard analyses could not reproduce the measured pressure responses well, and the calibrated hydraulic and two-phase parameters were not consistent with the preceding water test and laboratory analyses. Implementing the non-linear behaviour in terms of the observed relationship between changes in void ratio and associated changes in permeability under different stress conditions significantly improved the simulated results, resulting in a conceptual model that well reproduced the observed injection pressure and outflow responses for both tests, parallel and normal to bedding, using a consistent parameter set.
Validation Study of Genes with Hypermethylated Promoter Regions Associated with Prostate Cancer Recurrence
Authors: Stott-Miller Marni , Zhao Shanshan , Wright Jonathan L. , Kolb Suzanne , Bibikova Marina , Klotzle Brandy , Ostrander Elaine A. , Fan Jian-Bing , Feng Ziding , Stanford Janet L. 
Published: April 2014

Abstract
Background: One challenge in prostate cancer is distinguishing indolent from aggressive disease at diagnosis. DNA promoter hypermethylation is a frequent epigenetic event in prostate cancer, but few studies of DNA methylation in relation to features of more aggressive tumors or prostate cancer recurrence have been completed.
Methods: We used the Infinium HumanMethylation450 BeadChip to assess DNA methylation in tumor tissue from 407 patients with clinically localized prostate cancer who underwent radical prostatectomy. Recurrence status was determined by follow-up patient surveys, medical record review, and linkage with the Surveillance, Epidemiology, and End Results (SEER) registry. The methylation status of 14 genes for which promoter hypermethylation was previously correlated with advanced disease or biochemical recurrence was evaluated. Average methylation level for promoter region CpGs in patients who recurred compared with those with no evidence of recurrence was analyzed. For two genes with differential methylation, time to recurrence was examined.
Results: During an average follow-up of 11.7 years, 104 (26%) patients recurred. Significant promoter hypermethylation in at least 50% of CpG sites in two genes, ABHD9 and HOXD3, was found in tumors from patients who recurred compared with those without recurrence. Evidence was strongest for HOXD3 (lowest P = 9.46 × 10−6), with higher average methylation across promoter region CpGs associated with reduced recurrence-free survival (P = 2 × 10−4). DNA methylation profiles did not differ by recurrence status for the other genes.
Conclusions: These results validate the association between promoter hypermethylation of ADHB9 and HOXD3 and prostate cancer recurrence.
Impact: Tumor DNA methylation profiling may help to distinguish patients with prostate cancer at higher risk for disease recurrence. Cancer Epidemiol Biomarkers Prev; 23(7); 1331–9. ©2014 AACR.
Carnitine and Cardiac Dysfunction in Childhood Cancer Survivors Treated with Anthracyclines
Authors: Armenian Saro H. , Gelehrter Sarah K. , Vase Tabitha , Venkatramani Rajkumar , Landier Wendy , Wilson Karla D. , Herrera Claudia , Reichman Leah , Menteer John-David , Mascarenhas Leo , Freyer David R. , Venkataraman Kalyanasundaram , Bhatia Smita 
Published: April 2014

AbstractChildhood cancer survivors are at high risk of developing congestive heart failure (CHF) compared with the general population, and there is a dose-dependent increase in CHF risk by anthracycline dose. The mechanism by which this occurs has not been fully elucidated. Metabolomics, the comprehensive profile of small-molecule metabolites, has the potential to provide insight into the pathogenesis of disease states and discover diagnostic markers for therapeutic targets. We performed echocardiographic testing and blood plasma metabolomic analyses (8 pathways; 354 metabolites) in 150 asymptomatic childhood cancer survivors previously treated with anthracyclines. Median time from cancer diagnosis to study participation was 12.4 years (2.6–37.9 years); 64% were treated for a hematologic malignancy; median anthracycline dose was 350 mg/m2 (25–642 mg/m2). Thirty-five (23%) participants had cardiac dysfunction—defined as left ventricular end-systolic wall stress &gt;2SD by echocardiogram. Plasma levels of 15 compounds in three metabolic pathways (carbohydrate, amino acid, and lipid metabolism) were significantly different between individuals with cardiac dysfunction and those with normal systolic function. After adjusting for multiple comparisons, individuals with cardiac dysfunction had significantly lower plasma carnitine levels [relative ratio (RR), 0.89; P &lt; 0.01] in relation to those with normal systolic function. These findings may facilitate the development of primary prevention (treatment of carnitine deficiency before/during anthracycline administration) and secondary prevention strategies (screening and treatment in long-term survivors) in patients at highest risk for CHF. Cancer Epidemiol Biomarkers Prev; 23(6); 1109–14. ©2014 AACR.
Human tissue-type plasminogen activator
Authors: Kruithof Egbert K. O. , Dunoyer-Geindre Sylvie 
Published: April 2014

SummaryTissue-type plasminogen activator (t-PA ) plays an important role in the removal of intravascular fibrin deposits and has several physiological roles and pathological activities in the brain. Its production by many other cell types suggests that t-PA has additional functions outside the vascular and central nervous system. Activity of t-PA is regulated at the level of its gene transcription, its mRNA stability and translation, its storage and regulated release, its interaction with cofactors that enhance its activity, its inhibition by inhibitors such as plasminogen activator inhibitor type 1 or neuroserpin, and its removal by clearance receptors. Gene transcription of t-PA is modulated by a large number of hormones, growth factors, cytokines or drugs and t-PA gene responses may be tissue-specific. The aim of this review is to summarise current knowledge on t-PA function and regulation of its pericellular activity, with an emphasis on regulation of its gene expression.
A comparative cohort study on personalised antiplatelet therapy in PCI-treated patients with high on-clopidogrel platelet reactivity
Authors: Schulz Stefanie , Bernlochner Isabell , Morath Tanja , Braun Siegmund , Hausleiter Jörg , Massberg Steffen , Schunkert Heribert , Laugwitz Karl-Ludwig , Kastrati Adnan , Sibbing Dirk , Mayer Katharina 
Published: April 2014

SummaryIn clopidogrel-treated patients undergoing percutaneous coronary intervention (PCI), high platelet reactivity (HPR) is associated with a higher risk for thrombotic events including stent thrombosis (ST). A personalised therapy with selective intensification of treatment may improve HPR patients´ outcome in this setting although recent randomised trials are against this hypothesis. The aim of the ISAR-HPR registry was to assess whether clopidogrel-treated HPR patients benefit from selective intensification of P2Y12 receptor inhibition. For the registry, outcomes were compared between two cohorts. We identified 428 clopidogrel treated HPR patients (AU x min ≥468 on the Multiplate analyser) between 2007–2008 (historical control cohort) without a change of treatment based on platelet function (PF) testing results. Between 2009–2011, we identified 571 HPR patients (guided therapy cohort) and used this information for guidance and selective intensification of P2Y12 receptor directed treatment (reloading with clopidogrel, switch to prasugrel, re-testing) in a setting of routine PF testing. The primary outcome was the composite of death from any cause or ST after 30 days. Major bleeding according to TIMI criteria was also monitored. The incidence of the primary outcome was significantly lower in the guided vs the control cohort (7 [1.2%] vs 16 [3.7%] events; HR 0.32, 95% CI 0.13–0.79; p=0.009). The incidence of major bleeding was numerically but not statistically higher in the guided vs the control cohort (1.9 vs 0.7%; p=0.10). In conclusion, present findings are in support for a PF testing guided antiplatelet therapy with selective intensification of P2Y12 receptor inhibition. The issue of personalised antiplatelet treatment warrants further investigation in randomized and well-controlled clinical trials.
Factor Markets in Babylonia from the Late Seventh to the Third Century BCE
Authors: Jursa Michael 
Published: April 2014

Abstract
This paper studies the evidence for the existence of a labour market, a market for agricultural land, and a market for capital in Babylonia from the sixth to the third century bce. The argument is informed by our current understanding of the performance of Babylonian commodity markets, for which abundant quantitative information is available. I attempt to establish a connection between the general political and socio-economic development in Babylonia from the sixth century onwards and the increase and decrease of the role that can be attributed to factor markets.