bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Human Adenovirus Type 5 L4 Promoter Is Negatively Regulated by TFII-I and L4-33K
Authors: Wright Jordan , Atwan Zeenah , Morris Susan J. , Leppard Keith N. 
Published: April 2015

ABSTRACT
The late phase of adenovirus gene expression is controlled by proteins made in the intermediate phase, including L4 proteins of 22,000- and 33,000-Da apparent molecular mass (L4-22K and -33K proteins) that are expressed initially from the L4 promoter (L4P). The L4P is activated by a combination of viral proteins and cellular p53 and is ultimately inhibited again by its own products. Here, we have examined the L4P of human adenovirus type 5 in detail and have defined its transcription start site, which our data suggest is positioned by a weak TATA box. Rather than contributing positively to promoter activity, a putative initiator element at the transcription start site acts as a target for negative regulation imposed on the L4P by cellular TFII-I. We show that this TFII-I inhibition is relieved by one of the previously defined viral activators of the L4P, the E4 Orf3 protein, which alters the pool of TFII-I in the cell. We also explore further the negative regulation of the L4P by its products and show that the L4-33K protein is more significant in this process than L4-22K. It is the combined actions of positive and negative factors that lead to the transient activation of the L4P at the onset of the late phase of adenovirus gene expression.

IMPORTANCE
The adenovirus replication cycle proceeds through multiple phases of gene expression in which a key step is the activation of late-phase gene expression to produce proteins from which progeny particles can be formed. Working with human adenovirus type 5, we showed previously that two proteins expressed from the L4 region of the viral genome perform essential roles in moving the infection on into the late phase; these two proteins are produced by the action of a dedicated promoter, the L4P, and without them the infection does not proceed successfully to progeny generation. In this new work, we delineate further aspects of L4P activity and regulation. Understanding how the L4P works, and how it contributes to activation of the late phase of infection, is important to our understanding of natural infections by the virus, in which late gene expression can fail to occur, allowing the virus to persist.
A Combined Genetic-Proteomic Approach Identifies Residues within Dengue Virus NS4B Critical for Interaction with NS3 and Viral Replication
Authors: Chatel-Chaix Laurent , Fischl Wolfgang , Scaturro Pietro , Cortese Mirko , Kallis Stephanie , Bartenschlager Marie , Fischer Bernd , Bartenschlager Ralf 
Published: April 2015

ABSTRACTDengue virus (DENV) infection causes the most prevalent arthropod-borne viral disease worldwide. Approved vaccines are not available, and targets suitable for the development of antiviral drugs are lacking. One possible drug target is nonstructural protein 4B (NS4B), because it is absolutely required for virus replication; however, its exact role in the DENV replication cycle is largely unknown. With the aim of mapping NS4B determinants critical for DENV replication, we performed a reverse genetic screening of 33 NS4B mutants in the context of an infectious DENV genome. While the majority of these mutations were lethal, for several of them, we were able to select for second-site pseudoreversions, most often residing in NS4B and restoring replication competence. To identify all viral NS4B interaction partners, we engineered a fully viable DENV genome encoding an affinity-tagged NS4B. Mass spectrometry-based analysis of the NS4B complex isolated from infected cells identified the NS3 protease/helicase as a major interaction partner of NS4B. By combining the genetic complementation map of NS4B with a replication-independent expression system, we identified the NS4B cytosolic loop—more precisely, amino acid residue Q134—as a critical determinant for NS4B-NS3 interaction. An alanine substitution at this site completely abrogated the interaction and DENV RNA replication, and both were restored by pseudoreversions A69S and A137V. This strict correlation between the degree of NS4B-NS3 interaction and DENV replication provides strong evidence that this viral protein complex plays a pivotal role during the DENV replication cycle, hence representing a promising target for novel antiviral strategies.IMPORTANCEWith no approved therapy or vaccine against dengue virus infection, the viral nonstructural protein 4B (NS4B) represents a possible drug target, because it is indispensable for virus replication. However, little is known about its precise structure and function. Here, we established the first comprehensive genetic interaction map of NS4B, identifying amino acid residues that are essential for virus replication, as well as second-site mutations compensating for their defects. Additionally, we determined the NS4B viral interactome in infected cells and identified the NS3 protease/helicase as a major interaction partner of NS4B. We mapped residues in the cytosolic loop of NS4B as critical determinants for interaction with NS3, as well as RNA replication. The strong correlation between NS3-NS4B interaction and RNA replication provides strong evidence that this complex plays a pivotal role in the viral replication cycle, hence representing a promising antiviral drug target.
Activation and Regulation of DNA-Driven Immune Responses
Authors: Paludan Søren R. 
Published: April 2015

SUMMARY
The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally, several reports have demonstrated how defects in DNA sensing, signaling, and regulation are associated with susceptibility to infections or inflammatory diseases in humans and model organisms. In this review, the current literature on DNA-stimulated innate immune activation is discussed, and important new questions facing this field are proposed.
The cost-effectiveness of theMobileMumsintervention to increase physical activity among mothers with young children: a Markov model informed by a randomised controlled trial
Authors: Burn Edward , Marshall Alison L , Miller Yvette D , Barnett Adrian G , Fjeldsoe Brianna S , Graves Nicholas 
Published: April 2015

ObjectivesTo determine the cost-effectiveness of theMobileMumsintervention.MobileMumsis a 12-week programme which assists mothers with young children to be more physically active, primarily through the use of personalised SMS text-messages.DesignA cost-effectiveness analysis using a Markov model to estimate and compare the costs and consequences ofMobileMumsand usual care.SettingThis study considers the cost-effectiveness ofMobileMumsin Queensland, Australia.ParticipantsA hypothetical cohort of over 36 000 women with a child under 1 year old is considered. These women are expected to be eligible and willing to participate in the intervention in Queensland, Australia.Data sourcesThe model was informed by the effectiveness results from a 9-month two-arm community-based randomised controlled trial undertaken in 2011 and registered retrospectively with the Australian Clinical Trials Registry (ACTRN12611000481976). Baseline characteristics for the model cohort, treatment effects and resource utilisation were all informed by this trial.Main outcome measuresThe incremental cost per quality-adjusted life year (QALY) ofMobileMumscompared with usual care.ResultsThe intervention is estimated to lead to an increase of 131 QALYs for an additional cost to the health system of 1.1 million Australian dollars (AUD). The expected incremental cost-effectiveness ratio forMobileMumsis 8608 AUD per QALY gained.MobileMumshas a 98% probability of being cost-effective at a cost-effectiveness threshold of 64 000 AUD. Varying modelling assumptions has little effect on this result.ConclusionsAt a cost-effectiveness threshold of 64 000 AUD,MobileMumswould likely be a cost-effective use of healthcare resources in Queensland, Australia.Trial registration numberAustralian Clinical Trials Registry; ACTRN12611000481976.
Chemokine co-receptor usage in HIV-1-infected treatment-naïve voluntary counselling and testing clients in Southern Taiwan
Authors: Tsai Hung-Chin , Chou Pei-Yun , Wann Shue-Ren , Lee Susan Shin-Jung , Chen Yao-Shen 
Published: April 2015

ObjectiveThe goal of this present study was to determine the proportion of CCR5-tropic and CXCR4-tropic viruses and impact of tropism test on clinical presentation, CD4 cell counts, viral load and genotypic drug resistance from drug-naïve, voluntary counselling and testing (VCT) clients in southern Taiwan.DesignThis was a cross-sectional study. Plasma samples were collected from HIV-1-infected patients from January 2013 to December 2013; subjects were recruited from free VCT centres in southern Taiwan.SettingTaiwan.ParticipantsPlasma samples from 108 HIV-1-infected, treatment-naïve, VCT clients were analysed. HIV-1 strains were sequenced, genotype resistance was determined by a commercial kit (Viro-seq) and co-receptor tropism (CRT) was predicted by an internet tool geno2pheno[coreceptor], with a 10% false-positive rate as the cut-off. Differences in progression markers, patient characteristics, VCT questionnaires and HIV subtype distribution were evaluated statistically.ResultsAll the 108 VCT clients were male with 90% between the ages of 20 and 40 years. Eighty-eight per cent of the patients were men who have sex with men (MSM). The median (IQR) CD4 cell count was 342 cells/µL (221–454) and the viral load was 4.6 log (4.0–5.0). HIV-transmitted drug resistance was found in 9.3% (10/108) of the patients. CRT predictions indicated that 74% of the patients had only R5-tropic strains. CRT was not associated with CD4 cell counts, patient characteristics, VCT questionnaire and transmitted drug resistance. There was a significant difference with regard to viral load at the time of presentation, showing that patients with R5 more often had a higher viral load as compared with those with X4/DM strains (4.6±0.6 log vs 4.33±0.7 log, p=0.036).ConclusionsWe found that 74% of the VCT clients were infected with R5-tropic virus strains. HIV-transmitted drug resistance was not associated with CRT predictions. Higher viral load at presentation was predictive of R5 co-receptor usage.
Uncovering a missing demographic in trauma registries: epidemiology of trauma among American Indians and Alaska Natives in Washington State
Authors: Hoopes Megan J , Dankovchik Jenine , Weiser Thomas , Cheng Tabitha , Bigback Kristyn , Knaster Elizabeth S , Sugerman David E 
Published: April 2015

BackgroundThe objectives of this study were to evaluate racial misclassification in a statewide trauma registry and to describe the epidemiology of trauma among the Washington American Indian and Alaska Native (AI/AN) population.MethodsWe performed probabilistic record linkage between the Washington Trauma Registry (2005–2009) and Northwest Tribal Registry, a dataset of known AI/AN. AI/AN patients were compared with caucasians on demographic, injury and clinical outcome factors. A multivariable model estimated odds of mortality.ResultsRecord linkage increased ascertainment of AI/AN cases in the trauma registry 71%, from 1777 to 3039 cases. Compared with caucasians, AI/AN trauma patients were younger (mean age=36 vs 47 years, p<0.001) and more commonly male (66.5% vs 61.2%, p<0.001). AI/AN experienced more intentional injuries (suicide or homicide: 20.1% vs 6.7%, p<0.001), a higher proportion of severe traumatic brain injury (20.7% vs 16.8%, p=0.004) and were less likely than caucasians to use safety equipment such as seat belts/airbags (53.9% vs 76.7%, p<0.001). ISSs were similar (ISS >15: 21.4% vs 20.5%, p=0.63), and no difference was observed in mortality after adjustment for covariates (p=0.58).ConclusionsLinkage to a state trauma registry improved data quality by correcting racial misclassification, allowing for a comprehensive description of injury patterns for the AI/AN population. AI/AN sustained more severe injuries with similar postinjury outcomes to caucasians. Future efforts should focus on primary prevention for this population, including increased use of seat belts and child safety seats and reduction of interpersonal violence and suicide.
Differentiation of Papillary Muscle From Fascicular and Mitral Annular Ventricular Arrhythmias in Patients With and Without Structural Heart Disease
Authors: Al’Aref Subhi J. , Ip James E. , Markowitz Steven M. , Liu Christopher F. , Thomas George , Frenkel Daniel , Panda Nikhil C. , Weinsaft Jonathan W. , Lerman Bruce B. , Cheung Jim W. 
Published: April 2015

Background—
Idiopathic left ventricular arrhythmias (VAs) and those caused by structural heart disease can originate from the papillary muscles, fascicles, and mitral annulus. Differentiation of these arrhythmias can be challenging because they present with a right bundle branch block morphology by electrocardiography. We sought to identify clinical, electrocardiographic, and electrophysiological features that distinguish these left VAs in patients with and without structural heart disease.

Method and Results—

Patients undergoing catheter ablation for papillary muscle, fascicular, or mitral annular VAs were studied. Demographic data and electrocardiographic and electrophysiological findings were analyzed. Fifty-two VAs in 51 patients (32 [63%] male; mean age 61±15 years) with papillary muscle (n=18), fascicular (n=15), and mitral annular (n=19) origins were studied. Patients with papillary muscle VAs were older and had higher prevalence of left ventricular dysfunction (67% versus 13% of fascicular VA patients [
P
=0.009]) and coronary artery disease (78% versus 37% of mitral annular VA patients [
P
=0.036]). Papillary muscle VAs were distinguished electrocardiographically from fascicular VAs by longer QRS durations and lower prevalence of r<R′ V
1
QRS morphology, and from mitral annular VAs by lower prevalence of positive precordial lead concordance. Using a stepwise electrocardiographic algorithm, the accuracy rates for the diagnosis of papillary muscle VAs, fascicular VAs, and mitral annular VAs were 83%, 87%, and 89%, respectively.

Conclusions—
Specific electrocardiographic characteristics, including QRS morphology and precordial lead morphology, can help distinguish between papillary muscle, fascicular, and mitral annular VAs.
Incidence and Predictors of Cognitive Decline in Patients with Left Ventricular Assist Devices
Authors: Fendler Timothy J. , Spertus John A. , Gosch Kensey L. , Jones Philip G. , Bruce Jared M. , Nassif Michael E. , Flint Kelsey M. , Dunlay Shannon M. , Allen Larry A. , Arnold Suzanne V. 
Published: April 2015

Background—
After left ventricular assist device (LVAD) placement for advanced heart failure, increased cerebral perfusion should result in improved cognitive function. However, stroke (a well-known LVAD complication) and subclinical cerebral ischemia may result in transient or permanent cognitive decline. We sought to describe the incidence and predictors of cognitive decline after LVAD using a valid, sensitive assessment tool.

Methods and Results—

Among 4419 patients in the Interagency Registry for Mechanically Assisted Circulatory Support who underwent LVAD implantation between May 2012 and December 2013, cognitive function was assessed in 1173 patients with the Trail Making B Test before LVAD and at 3, 6, and 12 months. The test detects several forms of cognitive impairment, including subclinical stroke. Cognitive decline was defined as a clinically important increase during follow-up using a moderate Cohen
d
effect size of 0.5×baseline SD (32 s). The cumulative incidence of cognitive decline in the year after LVAD implantation, treating death and transplantation as competing risks, was 29.2%. In adjusted analysis, older age (≥70 versus <50 years; hazard ratio, 2.24; 95% confidence interval 1.46–3.44;
P
trend
<0.001) and destination therapy (hazard ratio, 1.42; 95% confidence interval, 1.05–1.92) were significantly associated with greater risk of cognitive decline.

Conclusions—
Cognitive decline occurs commonly in patients in the year after LVAD and is associated with older age and destination therapy. These results could have important implications for patient selection and improved communication of risks before LVAD implantation. Additional studies are needed to explore the association between cognitive decline and subsequent stroke, health status, and mortality in patients after LVAD.
Altered lymphopoiesis and immunodeficiency in miR-142 null mice
Authors: Kramer Nicholas J. , Wang Wei-Le , Reyes Estefany Y. , Kumar Bijender , Chen Ching-Cheng , Ramakrishna Chandran , Cantin Edouard M. , Vonderfecht Steven L. , Taganov Konstantin D. , Chau Nelson , Boldin Mark P. 
Published: April 2015

Key Points
miR-142 is an essential regulator of lymphocyte ontogenesis and is required for the generation of humoral and cellular immunity in mice. miR-142-3p regulates B-cell homeostasis by controlling expression of BAFF-R.
Association Between Low IQ Scores and Early Mortality in Men and Women: Evidence From a Population-Based Cohort Study
Authors: Maenner Matthew J , Greenberg Jan S , Mailick Marsha R 
Published: April 2015

Abstract
Lower (versus higher) IQ scores have been shown to increase the risk of early mortality, however, the underlying mechanisms are poorly understood and previous studies underrepresent individuals with intellectual disability (ID) and women. This study followed one third of all senior-year students (approximately aged 17) attending public high school in Wisconsin, U.S. in 1957 (n  =  10,317) until 2011. Men and women with the lowest IQ test scores (i.e., IQ scores ≤ 85) had increased rates of mortality compared to people with the highest IQ test scores, particularly for cardiovascular disease. Importantly, when educational attainment was held constant, people with lower IQ test scores did not have higher mortality by age 70 than people with higher IQ test scores. Individuals with lower IQ test scores likely experience multiple disadvantages throughout life that contribute to increased risk of early mortality.
The learning curve: Distinctive opportunities and challenges posed by university-based community radio stations
Authors: David Deborah Wilson 
Published: April 2015

Abstract
Siren FM is based at the University of Lincoln, in the centre of the historic cathedral city in the East Midlands, UK. It was one of the first full-time community radio stations to be founded by a British university and be fully located on the university’s campus. Once a student radio station, it was re-launched with a full community radio licence, with students forming one of the communities served. Using Siren FM as a case study, this article will document the challenges and potential benefits to operation and governance specific to a community radio station located on a university campus. It will look at the ways in which the station has been used as a mechanism for curriculum delivery and assessment, and explore how the students themselves engage with the station.
The article will argue that Siren FM, and other community radio stations that are located on university campuses, offer an interesting model for the relatively new third tier of radio in the UK, placing the stations in a unique position to effect social gain by enhancing students’ learning experience and empowering young people.
Online film circulation, copyright enforcement and the access to culture: The Italian case
Authors: Re Valentina 
Published: April 2015

Abstract
Despite the general emphasis on the positive implications of digital disruption in terms of freedom, democratization, disintermediation and cultural diversity, the digital impact on film production and distribution is more complex and nuanced, and maybe less disruptive, than what we would be inclined to believe. With respect to the effects of digital media on the film industry this article aims to provide an insight into film circulation in the digital environment, and into the multiple ways in which the Internet can affect and especially undermine the traditional system of film distribution. Based on this general framework, the article also aims to map the main features of contemporary Italian online distribution ecology, with particular reference to the quality of access to film culture and to the copyright issue. The article is structured into six sections. The first three sections provide a general contextualization and address in particular the relationships between the Internet and the window release system (Section 1), the question of piracy (Section 2), the changes in gatekeeping mechanisms and patterns of demand, and the issue of access (Section 3). The remaining three sections focus on the Italian context: Section 4 presents the main theoretical categories used to map contemporary Italian online film distribution; Section 5 discusses the main features of the map; finally, Section 6 provides an insight into the current legal framework and scope of the new Italian ‘Regulation about copyright protection in electronic communication networks’, ratified by AGCOM in December 2013.
From documentary truth to historical evidence: The images of the Genoa G8 protests and the construction of public memory
Authors: Capelli Claudia 
Published: April 2015

Abstract
This article looks at the process of construction of a national memory of the 2001 Genoa G8 Summit Conference in Italy through the analysis of the audio-visual documentation of the event and of the meanings and forms it has acquired over the years. I argue that the context of production of these documents and the prolonged conflict over their interpretation has made them a fundamental element for the public memory of the event. In fact, the specificities of this case make it comparable to other divisive historical events that have represented ‘difficult pasts’ or ‘cultural traumas’ for entire nations, and can therefore be analysed within the same theoretical framework. In particular, I examine the documentaries produced by Global Justice Movement activists in the wake of the two days of violence and riots that accompanied the works of the conference, and the first docudrama to be entirely dedicated to the event, Diaz. Don’t Clean Up This Blood (2012) by Daniele Vicari.
Exploring Aggressive Legalism: Is Now A Good Time to Promote This Approach in Greater Asia?
Authors: Lu Yi 
Published: April 2015

Abstract
Aggressive legalism, a trade policy-making strategy targeted at actively utilizing WTO rules to defend trade interests, has greatly benefited major Eastern Asian countries in past years. This paper examines whether this strategy should be promoted around greater Asia in this era. First, this paper updates the status of adoption of aggressive legalism in East Asian countries including Japan, Korea and China. Second, it looks into the current and possible future utilization of the WTO Dispute Settlement Mechanism by selected countries which are frequent “targets” of trade remedy measures, namely India, Thailand and Indonesia. Finally, it discusses the participation of Asian developing countries in the WTO. Relying upon case studies and statistical analysis, the author finds that Asian countries’ rising image in international trade signals a trend of adopting aggressive legalism in Great Asia. This trend will undoubtedly promote the energetic development of international trade globally. However, room for more progressive participation in the WTO still exists, especially in developing countries.