bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avian Leukosis Virus Activation of an Antisense RNA Upstream of
TERT
in B-Cell Lymphomas
Authors: Nehyba Jiri , Malhotra Sanandan , Winans Shelby , O'Hare Thomas H. , Justice James , Beemon Karen 
Published: August 2016

ABSTRACT

Avian leukosis virus (ALV) induces tumors by integrating its proviral DNA into the chicken genome and altering the expression of nearby genes via strong promoter and enhancer elements. Viral integration sites that contribute to oncogenesis are selected in tumor cells. Deep-sequencing analysis of B-cell lymphoma DNA confirmed that the telomerase reverse transcriptase (
TERT
) gene promoter is a common ALV integration target. Twenty-six unique proviral integration sites were mapped between 46 and 3,552 nucleotides (nt) upstream of the
TERT
transcription start site, predominantly in the opposite transcriptional orientation to
TERT
. Transcriptome-sequencing (RNA-seq) analysis of normal bursa revealed a transcribed region upstream of
TERT
in the opposite orientation, suggesting the
TERT
promoter is bidirectional. This transcript appears to be an uncharacterized antisense RNA. We have previously shown that
TERT
expression is upregulated in tumors with integrations in the
TERT
promoter region. We now report that the viral promoter drives the expression of a chimeric transcript containing viral sequences spliced to exons 4 through 7 of this antisense RNA. Clonal expansion of cells with ALV integrations driving overexpression of the
TERT
antisense RNA suggest it may have a role in tumorigenesis.

IMPORTANCE
The data suggest that ALV integrations in the TERT promoter region drive the overexpression of a novel antisense RNA and contribute to the development of lymphomas.
Influenza A Virus Infection in Pigs Attracts Multifunctional and Cross-Reactive T Cells to the Lung
Authors: Talker Stephanie C. , Stadler Maria , Koinig Hanna C. , Mair Kerstin H. , Rodríguez-Gómez Irene M. , Graage Robert , Zell Roland , Dürrwald Ralf , Starick Elke , Harder Timm , Weissenböck Herbert , Lamp Benjamin , Hammer Sabine E. , Ladinig Andrea , Saalmüller Armin , Gerner Wilhelm 
Published: August 2016

ABSTRACTPigs are natural hosts for influenza A viruses and play a critical role in influenza epidemiology. However, little is known about their influenza-evoked T-cell response. We performed a thorough analysis of both the local and systemic T-cell response in influenza virus-infected pigs, addressing kinetics and phenotype as well as multifunctionality (gamma interferon [IFN-γ], tumor necrosis factor alpha [TNF-α], and interleukin-2 [IL-2]) and cross-reactivity. A total of 31 pigs were intratracheally infected with an H1N2 swine influenza A virus (FLUAVsw) and consecutively euthanized. Lungs, tracheobronchial lymph nodes, and blood were sampled during the first 15 days postinfection (p.i.) and at 6 weeks p.i.Ex vivoflow cytometry of lung lymphocytes revealed an increase in proliferating (Ki-67+) CD8+T cells with an early effector phenotype (perforin+CD27+) at day 6 p.i. Low frequencies of influenza virus-specific IFN-γ-producing CD4+and CD8+T cells could be detected in the lung as early as 4 days p.i. On consecutive days, influenza virus-specific CD4+and CD8+T cells produced mainly IFN-γ and/or TNF-α, reaching peak frequencies around day 9 p.i., which were up to 30-fold higher in the lung than in tracheobronchial lymph nodes or blood. At 6 weeks p.i., CD4+and CD8+memory T cells had accumulated in lung tissue. These cells showed diverse cytokine profiles andin vitroreactivity against heterologous influenza virus strains, all of which supports their potential to combat heterologous influenza virus infections in pigs.IMPORTANCEPigs not only are a suitable large-animal model for human influenza virus infection and vaccine development but also play a central role in the emergence of new pandemic strains. Although promising candidate universal vaccines are tested in pigs and local T cells are the major correlate of heterologous control, detailed and targeted analyses of T-cell responses at the site of infection are scarce. With the present study, we provide the first detailed characterization of magnitude, kinetics, and phenotype of specific T cells recruited to the lungs of influenza virus-infected pigs, and we could demonstrate multifunctionality, cross-reactivity, and memory formation of these cells. This, and ensuing work in the pig, will strengthen the position of this species as a large-animal model for human influenza virus infection and will immediately benefit vaccine development for improved control of influenza virus infections in pigs.
Benign Rabbit Caliciviruses Exhibit Evolutionary Dynamics Similar to Those of Their Virulent Relatives
Authors: Mahar Jackie E. , Nicholson Leila , Eden John-Sebastian , Duchêne Sebastián , Kerr Peter J. , Duckworth Janine , Ward Vernon K. , Holmes Edward C. , Strive Tanja 
Published: August 2016

ABSTRACT

Two closely related caliciviruses cocirculate in Australia: rabbit hemorrhagic disease virus (RHDV) and rabbit calicivirus Australia 1 (RCV-A1). RCV-A1 causes benign enteric infections in the European rabbit (
Oryctolagus cuniculus
) in Australia and New Zealand, while its close relative RHDV causes a highly pathogenic infection of the liver in the same host. The comparison of these viruses provides important information on the nature and trajectory of virulence evolution, particularly as highly virulent strains of RHDV may have evolved from nonpathogenic ancestors such as RCV-A1. To determine the evolution of RCV-A1 we sequenced the full-length genomes of 44 RCV-A1 samples isolated from healthy rabbits and compared key evolutionary parameters to those of its virulent relative, RHDV. Despite their marked differences in pathogenicity and tissue tropism, RCV-A1 and RHDV have evolved in a very similar manner. Both viruses have evolved at broadly similar rates, suggesting that their dynamics are largely shaped by high background mutation rates, and both exhibit occasional recombination and an evolutionary environment dominated by purifying selection. In addition, our comparative analysis revealed that there have been multiple changes in both virulence and tissue tropism in the evolutionary history of these and related viruses. Finally, these new genomic data suggest that either RCV-A1 was introduced into Australia after the introduction of myxoma virus as a biocontrol agent in 1950 or there was drastic reduction of the rabbit population, and hence of RCV-A1 genetic diversity, perhaps coincident with the emergence of myxoma virus.

IMPORTANCE
The comparison of closely related viruses that differ profoundly in propensity to cause disease in their hosts offers a powerful opportunity to reveal the causes of changes in virulence and to study how such changes alter the evolutionary dynamics of these pathogens. Here we describe such a novel comparison involving two closely related RNA viruses that cocirculate in Australia, the highly virulent rabbit hemorrhagic disease virus (RHDV) and the nonpathogenic rabbit calicivirus Australia 1 (RCV-A1). Both viruses infect the European rabbit, but they differ in virulence, tissue tropism, and mechanisms of transmission. Surprisingly, and despite these fundamental differences, RCV-A1 and RHDV have evolved at very similar (high) rates and with strong purifying selection. Furthermore, candidate key mutations were identified that may play a role in virulence and/or tissue tropism and therefore warrant further investigation.
Identification of Residues That Affect Oligomerization and/or Enzymatic Activity of Influenza Virus H5N1 Neuraminidase Proteins
Authors: Dai Meiling , Guo Hongbo , Dortmans Jos C. F. M. , Dekkers Jojanneke , Nordholm Johan , Daniels Robert , van Kuppeveld Frank J. M. , de Vries Erik , de Haan Cornelis A. M. 
Published: August 2016

ABSTRACT

Influenza A virus (IAV) attachment to and release from sialoside receptors is determined by the balance between hemagglutinin (HA) and neuraminidase (NA). The molecular determinants that mediate the specificity and activity of NA are still poorly understood. In this study, we aimed to design the optimal recombinant soluble NA protein to identify residues that affect NA enzymatic activity. To this end, recombinant soluble versions of four different NA proteins from H5N1 viruses were compared with their full-length counterparts. The soluble NA ectodomains were fused to three commonly used tetramerization domains. Our results indicate that the particular oligomerization domain used does not affect the

K
m

value but may affect the specific enzymatic activity. This particularly holds true when the stalk domain is included and for NA ectodomains that display a low intrinsic ability to oligomerize. NA ectodomains extended with a Tetrabrachion domain, which forms a nearly parallel four-helix bundle, better mimicked the enzymatic properties of full-length proteins than when other coiled-coil tetramerization domains were used, which probably distort the stalk domain. Comparison of different NA proteins and mutagenic analysis of recombinant soluble versions thereof resulted in the identification of several residues that affected oligomerization of the NA head domain (position 95) and therefore the specific activity or sialic acid binding affinity (

K
m

value; positions 252 and 347). This study demonstrates the potential of using recombinant soluble NA proteins to reveal determinants of NA assembly and enzymatic activity.

IMPORTANCE
The IAV HA and NA glycoproteins are important determinants of host tropism and pathogenicity. However, NA is relatively understudied compared to HA. Analysis of soluble versions of these glycoproteins is an attractive way to study their activities, as they are easily purified from cell culture media and applied in downstream assays. In the present study, we analyzed the enzymatic activity of different NA ectodomains with three commonly used tetramerization domains and compared them with full-length NA proteins. By performing a mutagenic analysis, we identified several residues that affected NA assembly, activity, and/or substrate binding. In addition, our results indicate that the design of the recombinant soluble NA protein, including the particular tetramerization domain, is an important determinant for maintaining the enzymatic properties within the head domain. NA ectodomains extended with a Tetrabrachion domain better mimicked the full-length proteins than when the other tetramerization domains were used.
NF-κB and IRF1 Induce Endogenous Retrovirus K Expression via Interferon-Stimulated Response Elements in Its 5′ Long Terminal Repeat
Authors: Manghera Mamneet , Ferguson-Parry Jennifer , Lin Rongtuan , Douville Renée N. 
Published: August 2016

ABSTRACTThousands of endogenous retroviruses (ERV), viral fossils of ancient germ line infections, reside within the human genome. Evidence of ERV activity has been observed widely in both health and disease. While this is most often cited as a bystander effect of cell culture or disease states, it is unclear which signals control ERV transcription. Bioinformatic analysis suggests that the viral promoter of endogenous retrovirus K (ERVK) is responsive to inflammatory transcription factors. Here we show that one reason for ERVK upregulation in amyotrophic lateral sclerosis (ALS) is the presence of functional interferon-stimulated response elements (ISREs) in the viral promoter. Transcription factor overexpression assays revealed independent and synergistic upregulation of ERVK by interferon regulatory factor 1 (IRF1) and NF-κB isoforms. Tumor necrosis factor alpha (TNF-α) and LIGHT cytokine treatments of human astrocytes and neurons enhanced ERVK transcription and protein levels through IRF1 and NF-κB binding to the ISREs. We further show that in ALS brain tissue, neuronal ERVK reactivation is associated with the nuclear translocation of IRF1 and NF-κB isoforms p50 and p65. ERVK overexpression can cause motor neuron pathology in murine models. Our results implicate neuroinflammation as a key trigger of ERVK provirus reactivation in ALS. These molecular mechanisms may also extend to the pathobiology of other ERVK-associated inflammatory diseases, such as cancers, HIV infection, rheumatoid arthritis, and schizophrenia.IMPORTANCEIt has been well established that inflammatory signaling pathways in ALS converge at NF-κB to promote neuronal damage. Our findings suggest that inflammation-driven IRF1 and NF-κB activity promotes ERVK reactivation in neurons of the motor cortex in ALS. Thus, quenching ERVK activity through antiretroviral or immunomodulatory regimens may hinder virus-mediated neuropathology and improve the symptoms of ALS or other ERVK-associated diseases.
Comparison of the NBM 200 non-invasive haemoglobin sensor with Sahli's haemometer among adolescent girls in rural India
Authors: Ahankari A S , Dixit J V , Fogarty A W , Tata L J , Myles P R 
Published: August 2016

ObjectiveThe study objective was to compare haemoglobin (Hb) measurements between the NBM 200 (non-invasive Hb sensor) and Sahli's haemometer in adolescent girls in a rural Indian setting.MethodsParticipants included girls aged between 13 and 17 years from 34 villages in Tuljapur and Lohara blocks of Osmanabad district, Maharashtra, India. Hb measurements from the non-invasive sensor (NBM 200) were compared with measurements obtained from Sahli's haemometer using the Bland-Altman plot, Spearman correlation coefficient, sensitivity, specificity and area under the receiver operating characteristic curve analysis (AUROC).ResultsPaired measurements from both methods were obtained from 766 adolescent girls (N=766). Hb levels estimated by Sahli's haemometer ranged from 5.0 to 14.0 g/dL (mean 10.1 g/dL, SD 1.41), whereas measurements obtained from the NBM 200 ranged from 9.5 to 15.2 g/dL (mean 12.8 g/dL, SD 1.42). The Bland-Altman analysis indicated a mean difference of −2.70 g/dL (95% CI −2.84 to −2.55) demonstrating an overestimation of Hb measurement by the NBM 200 compared with the Sahli's haemometer measurements. The NBM 200 showed low sensitivity (23.6%) and moderate specificity (61.8%) for the diagnosis of anaemia. The AUROC score was 0.43 indicating an underestimation of anaemia in our study population by the NBM 200.ConclusionsHb measurements obtained from the NBM 200 were consistently higher leading to an underestimation of prevalence of anaemia compared with Sahli's haemometer estimates among adolescent girls in India.
Impact of an SMS advice programme on maternal and newborn health in rural China: study protocol for a quasi-randomised controlled trial
Authors: Su Yanfang , Yuan Changzheng , Zhou Zhongliang , Heitner Jesse , Campbell Benjamin 
Published: August 2016

IntroductionExpectant mothers in low-income and middle-income countries often lack access to vital information about pregnancy, preparation for birth and best practices when caring for their newborn. Innovative solutions are needed to bridge this knowledge gap and dramatically improve maternal and neonatal health in these settings. This study aims to evaluate the impact of an innovative text messaging intervention on maternal and neonatal health outcomes.Methods and analysisThis study offers expectant mothers in rural China a package of free short messages via cell phone regarding pregnancy and childbirth. These messages are tailored to each mother's gestational week. It is hypothesised that delivering these short advice messages to pregnant women can improve maternal and newborn health. The study uses factorial quasi-randomisation to compare psychological, behavioural and health outcomes between 4 groups: 2 groups receiving different sets of short message interventions (ie, good household prenatal practices and healthcare seeking), a group receiving both interventions and a control group. Treatment assignment occurs at the individual level. The primary outcome is newborn health, measured by appropriateness of weight for gestational age. Secondary outcomes include severe neonatal and maternal morbidity as well as psychological and behavioural measures. This study has enrolled pregnant women who attend county maternal and child health centres for their prenatal visits.DiscussionThis pilot is the first large-scale effort to build a comprehensive evidence base on the impact of prenatal text messages via cell phone on maternal and newborn health outcomes in China. The study has broad implications for public health policy in China and the implementation of mobile health interventions in low-resource settings around the world.EthicsThis study was approved by the Ethics Committee of the School of Medicine at Xi'an Jiaotong University on 18 January 2013.Trial registration numberNCT02037087; Pre-results.
Cancer symptom scale preferences: does one size fit all?
Authors: Jeter Kirby , Blackwell Siobhan , Burke Lucy , Joyce David , Moran Catherine , Conway Emma Victoria , Cremen Iseult , O'Connor Brenda , Ui Dhuibhir Pauline , Walsh Declan 
Published: August 2016

ObjectivesPatients with advanced cancer do not report all symptoms, so assessment is best done systematically. However, for such patients, completion rates of some symptom instruments are <50%. Symptoms can be quantified by various scales including the Categorical Response Scale (CRS), Numerical Rating Scale (NRS) and Visual Analogue Scale (VAS). Patient preferences for CRS, NRS and VAS in symptom assessment and their clinical utility in 3 cancer symptoms: pain, tiredness and appetite loss were determined.MethodsA prospective survey was conducted involving cancer admissions to a 36-bed palliative care unit.Results100 inpatients were recruited, aged 38–93 years (x̅ =71 years; SD=11.6), with median Eastern Cooperative Oncology Group (ECOG) scores of 2 (range 0–4). VAS was the least preferred measure. 52% of patients choose the same scale for all 3 symptoms and 44% for 2, with 4% choosing a different individual scale per symptom. There was moderate agreement between participant scale preference and observer determined ease of scale completion (loss of appetite: κ=0.36; pain: κ=0.49; tiredness: κ=0.45). Participants preferred CRS for appetite loss (48%) and tiredness (40%) and NRS for pain (44%).ConclusionsVAS was the least favoured scale and should be used cautiously in this population. Most participants had a scale preference with high intrapatient consistency between scales. CRS was preferred for appetite loss and tiredness and NRS for pain. Consideration should be given to individualised cancer symptom assessment according to patient scale preference.
Establishing an injury indicator for severe paediatric injury
Authors: Pike Ian , Khalil Mina , Yanchar Natalie L , Tamim Hala , Nathens Avery B , Macpherson Alison K 
Published: August 2016

BackgroundRoutinely gathered injury data, such as hospitalisations, may be subject to variation from sources other than injury incidence. There is a need for an indicator that defines severe injury, which may be less vulnerable to fluctuations due to changes in care policies. The purpose of this study was to identify International Classification of Diseases-10 codes associated with severe paediatric injuries and to specify and validate a severe paediatric injury indicator.MethodsTwo data sets that included the ISS and the survival risk ratio were used to produce a list of diagnoses to define severe paediatric injury. The list was sent to trauma surgeons who classified each code as severe enough or not severe enough to require care in a trauma centre. The indicator was fully specified, then validated by using a different data set to validate the codes in a real-world situation.ResultsSixty diagnoses were identified as representing severe paediatric injury. Following specification, the indicator was applied to an existing comprehensive data set of paediatric injuries. The decline in hospitalisation of paediatric injuries was significantly steeper for severe than non-severe injuries, suggesting that factors related to the decline in this trauma subset are unlikely to be related to changes in access or other components of trauma care delivery.ConclusionsThis indicator can be used for the evaluation of trends in severe paediatric trauma and will help identify populations at risk. This research may inform policies and procedures for referrals of severe childhood injury to appropriate levels of care.
Confusa e irritante multidão de livros: relações entre o contexto histórico-informacional da Europa Moderna e a estrutura documentária de Bibliotheca Universalis, de Conrad Gesner
Authors: Araujo Andre Vieira de Freitas , Crippa Giulia 
Published: August 2016

A Imprensa teve como um dos seus mais significativos impactos a vasta, intensa e acelerada produção de bibliografias, como meios de registro, organização, seleção, disponibilização e mediação de documentos. Entre as inúmeras conseqüências da Imprensa está a necessidade de se operar a chamada explosão informacional - fenômeno investigado, do ponto de vista histórico-cultural, por autores como Peter Burke e Ann Blair. A partir desta paisagem, o artigo busca estabelecer relações entre o contexto histórico-informacional da Europa Moderna e Bibliotheca Universalis, de Conrad Gesner (Séc. XVI). Bibliotheca arrola aspectos da cultura manuscrita e impressa e traz implicitamente uma profunda reflexão descritiva e semântica sobre os documentos e os saberes, conforme se evidencia nos estudos de Alfredo Serrai e Fiammetta Sabba. O “gesto bibliográfico” gesneriano é mais do que uma resposta a confusa et noxia illa librorum multitude (“confusa e irritante multidão de livros”, que hoje nos remete ao sentido da denominada information overload): é a força que arquiteta a própria Bibliografia enquanto disciplina.
Cardiac Magnetic Resonance–Measured Left Atrial Volume and Function and Incident Atrial Fibrillation
Authors: Habibi Mohammadali , Samiei Sanaz , Ambale Venkatesh Bharath , Opdahl Anders , Helle-Valle Thomas M. , Zareian Mytra , Almeida Andre L.C. , Choi Eui-Young , Wu Colin , Alonso Alvaro , Heckbert Susan R. , Bluemke David A. , Lima João A.C. 
Published: August 2016

Background—
Early detection of structural changes in left atrium (LA) before atrial fibrillation (AF) development could be helpful in identification of those at higher risk for AF. Using cardiac magnetic resonance imaging, we examined the association of LA volume and function, and incident AF in a multiethnic population free of clinical cardiovascular diseases.

Methods and Results—
In a case–cohort study embedded in MESA (Multi-Ethnic Study of Atherosclerosis), baseline LA size and function assessed by cardiac magnetic resonance feature-tracking were compared between 197 participants with incident AF and 322 participants randomly selected from the whole MESA cohort. Participants were followed up for 8 years. Incident AF cases had a larger LA volume and decreased passive, active, and total LA emptying fractions and peak global LA longitudinal strain (peak LA strain) at baseline. In multivariable analysis, elevated LA maximum volume index (hazard ratio, 1.38 per SD; 95% confidence interval, 1.01–1.89) and decreased peak LA strain (hazard ratio, 0.68 per SD; 95% confidence interval, 0.48–0.96), and passive and total LA emptying fractions (hazard ratio for passive LA emptying fractions, 0.55 per SD; 95% confidence interval, 0.40–0.75 and hazard ratio for active LA emptying fractions, 0.70 per SD; 95% confidence interval, 0.52–0.95), but not active LA emptying fraction, were associated with incident AF.

Conclusions—
Elevated LA volumes and decreased passive and total LA emptying fractions were independently associated with incident AF in an asymptomatic multiethnic population. Including LA functional variables along with other risk factors of AF may help to better risk stratify individuals at risk of AF development.