bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the Determinants of NS2-3-Independent Virion Morphogenesis of Pestiviruses
Authors: Klemens O. , Dubrau D. , Tautz N. 
Published: September 2015

ABSTRACTA peculiarity of theFlaviviridaeis the critical function of nonstructural (NS) proteins for virus particle formation. For pestiviruses, like bovine viral diarrhea virus (BVDV), uncleaved NS2-3 represents an essential factor for virion morphogenesis, while NS3 is an essential component of the viral replicase. Accordingly, in natural pestivirus isolates, processing at the NS2-3 cleavage site is not complete, to allow for virion morphogenesis. Virion morphogenesis of the related hepatitis C virus (HCV) shows a major deviation from that of pestiviruses: while RNA replication also requires free NS3, virion formation does not depend on uncleaved NS2-NS3. Recently, we described a BVDV-1 chimera based on strain NCP7 encompassing the NS2-4B*-coding region of strain Osloss (E. Lattwein, O. Klemens, S. Schwindt, P. Becher, and N. Tautz, J Virol 86:427–437, 2012, doi:10.1128/JVI.06133-11). This chimera allowed for the production of infectious virus particles in the absence of uncleaved NS2-3. The Osloss sequence deviates in the NS2-4B* part from NCP7 in 48 amino acids and also has a ubiquitin insertion between NS2 and NS3. The present study demonstrates that in the NCP7 backbone, only two amino acid exchanges in NS2 (E1576V) and NS3 (V1721A) are sufficient and necessary to allow for efficient NS2-3-independent virion morphogenesis. The adaptation of a bicistronic virus encompassing an internal ribosomal entry site element between the NS2 and NS3 coding sequences to efficient virion morphogenesis led to the identification of additional amino acids in E2, NS2, and NS5B that are critically involved in this process. The surprisingly small requirements for approximating the packaging schemes of pestiviruses and HCV with respect to the NS2-3 region is in favor of a common mechanism in an ancestral virus.IMPORTANCEFor positive-strand RNA viruses, the processing products of the viral polyprotein serve in RNA replication as well as virion morphogenesis. For bovine viral diarrhea virus, nonstructural protein NS2-3 is of critical importance to switch between these processes. While free NS3 is essential for RNA replication, uncleaved NS2-3, which accumulates over time in the infected cell, is required for virion morphogenesis. In contrast, the virion morphogenesis of the related hepatitis C virus is independent from uncleaved NS2-NS3. Here, we demonstrate that pestiviruses can adapt to virion morphogenesis in the absence of uncleaved NS2-3 by just two amino acid exchanges. While the mechanism behind this gain of function remains elusive, the fact that it can be achieved by such minor changes is in line with the assumption that an ancestral virus already used this mechanism but lost it in the course of adapting to a new host/infection strategy.
Virus Multiplicity of Infection Affects Type I Interferon Subtype Induction Profiles and Interferon-Stimulated Genes
Authors: Zaritsky Luna A. , Bedsaul Jacquelyn R. , Zoon Kathryn C. 
Published: September 2015

ABSTRACT
Type I interferons (IFNs) are induced upon viral infection and important mediators of innate immunity. While there is 1 beta interferon (IFN-β) protein, there are 12 different IFN-α subtypes. It has been reported extensively that different viruses induce distinct patterns of IFN subtypes, but it has not been previously shown how the viral multiplicity of infection (MOI) can affect IFN induction. In this study, we discovered the novel finding that human U937 cells infected with 2 different concentrations of Sendai virus (SeV) induce 2 distinct type I IFN subtype profiles. Cells infected at the lower MOI induced more subtypes than cells infected at the higher MOI. We found that this was due to the extent of signaling through the IFN receptor (IFNAR). The cells infected at the lower viral MOI induced the IFNAR2-dependent IFN-α subtypes 4, 6, 7, 10, and 17, which were not induced in cells infected at higher virus concentrations. IFN-β and IFN-α1, -2, and -8 were induced in an IFNAR-independent manner in cells infected at both virus concentrations. IFN-α5, -14, -16, and -21 were induced in an IFNAR-dependent manner in cells infected at lower virus concentrations and in an IFNAR-independent manner in cells infected at higher virus concentrations. These differences in IFN subtype profiles in the 2 virus concentrations also resulted in distinct interferon-stimulated gene induction. These results present the novel finding that different viral MOIs differentially activate JAK/STAT signaling through the IFNAR, which greatly affects the profile of IFN subtypes that are induced.

IMPORTANCE
Type I IFNs are pleiotropic cytokines that are instrumental in combating viral diseases. Understanding how the individual subtypes are induced is important in developing strategies to block viral replication. Many studies have reported that different viruses induce distinct type I IFN subtype profiles due to differences in the way viruses are sensed in different cell types. However, we report in our study the novel finding that the amount of virus used to infect a system can also affect which type I IFN subtypes are induced due to the extent of activation of certain signaling pathways. These distinct IFN subtype profiles in cells infected at different MOIs are correlated with differences in interferon-stimulated gene induction, indicating that the same virus can induce distinct antiviral responses depending on the MOI. Because type I IFNs are used as therapeutic agents to treat viral diseases, understanding their antiviral mechanisms can enhance clinical treatments.
Sulfolobus Spindle-Shaped Virus 1 Contains Glycosylated Capsid Proteins, a Cellular Chromatin Protein, and Host-Derived Lipids
Authors: Quemin Emmanuelle R. J. , Pietilä Maija K. , Oksanen Hanna M. , Forterre Patrick , Rijpstra W. Irene C. , Schouten Stefan , Bamford Dennis H. , Prangishvili David , Krupovic Mart 
Published: September 2015

ABSTRACT

Geothermal and hypersaline environments are rich in virus-like particles, among which spindle-shaped morphotypes dominate. Currently, viruses with spindle- or lemon-shaped virions are exclusive to
Archaea
and belong to two distinct viral families. The larger of the two families, the
Fuselloviridae
, comprises tail-less, spindle-shaped viruses, which infect hosts from phylogenetically distant archaeal lineages.
Sulfolobus
spindle-shaped virus 1 (SSV1) is the best known member of the family and was one of the first hyperthermophilic archaeal viruses to be isolated. SSV1 is an attractive model for understanding virus-host interactions in
Archaea
; however, the constituents and architecture of SSV1 particles remain only partially characterized. Here, we have conducted an extensive biochemical characterization of highly purified SSV1 virions and identified four virus-encoded structural proteins, VP1 to VP4, as well as one DNA-binding protein of cellular origin. The virion proteins VP1, VP3, and VP4 undergo posttranslational modification by glycosylation, seemingly at multiple sites. VP1 is also proteolytically processed. In addition to the viral DNA-binding protein VP2, we show that viral particles contain the
Sulfolobus solfataricus
chromatin protein Sso7d. Finally, we provide evidence indicating that SSV1 virions contain glycerol dibiphytanyl glycerol tetraether (GDGT) lipids, resolving a long-standing debate on the presence of lipids within SSV1 virions. A comparison of the contents of lipids isolated from the virus and its host cell suggests that GDGTs are acquired by the virus in a selective manner from the host cytoplasmic membrane, likely during progeny egress.

IMPORTANCE
Although spindle-shaped viruses represent one of the most prominent viral groups in
Archaea
, structural data on their virion constituents and architecture still are scarce. The comprehensive biochemical characterization of the hyperthermophilic virus SSV1 presented here brings novel and significant insights into the organization and architecture of spindle-shaped virions. The obtained data permit the comparison between spindle-shaped viruses residing in widely different ecological niches, improving our understanding of the adaptation of viruses with unusual morphotypes to extreme environmental conditions.
Technical efficiency and productivity of Chinese county hospitals: an exploratory study in Henan province, China
Authors: Cheng Zhaohui , Tao Hongbing , Cai Miao , Lin Haifeng , Lin Xiaojun , Shu Qin , Zhang Ru-ning 
Published: September 2015

ObjectivesChinese county hospitals have been excessively enlarging their scale during the healthcare reform since 2009. The purpose of this paper is to examine the technical efficiency and productivity of county hospitals during the reform process, and to determine whether, and how, efficiency is affected by various factors.Setting and participants114 sample county hospitals were selected from Henan province, China, from 2010 to 2012.Outcome measuresData envelopment analysis was employed to estimate the technical and scale efficiency of sample hospitals. The Malmquist index was used to calculate productivity changes over time. Tobit regression was used to regress against 4 environmental factors and 5 institutional factors that affected the technical efficiency.Results(1) 112 (98.2%), 112 (98.2%) and 104 (91.2%) of the 114 sample hospitals ran inefficiently in 2010, 2011 and 2012, with average technical efficiency of 0.697, 0.748 and 0.790, respectively. (2) On average, during 2010–2012, productivity of sample county hospitals increased by 7.8%, which was produced by the progress in technical efficiency changes and technological changes of 0.9% and 6.8%, respectively. (3) Tobit regression analysis indicated that government subsidy, hospital size with above 618 beds and average length of stay assumed a negative sign with technical efficiency; bed occupancy rate, ratio of beds to nurses and ratio of nurses to physicians assumed a positive sign with technical efficiency.ConclusionsThere was considerable space for technical efﬁciency improvement in Henan county hospitals. During 2010–2012, sample hospitals experienced productivity progress; however, the adverse change in pure technical efficiency should be emphasised. Moreover, according to the Tobit results, policy interventions that strictly supervise hospital bed scale, shorten the average length of stay and coordinate the proportion among physicians, nurses and beds, would benefit hospital efficiency.
Clinical and economic characteristics of emergency department visits due to acetaminophen toxicity in the USA
Authors: Altyar Ahmed , Kordi Lama , Skrepnek Grant 
Published: September 2015

ObjectivesTo estimate the number of acetaminophen (APAP) toxicity-related emergency department (ED) visits, and to assess their associated clinical and economic burden in the USA from 2006 to 2010.DesignCross-sectional, retrospective, large-scale database study.SettingNon-federal, non-rehabilitation, community EDs in the USA.ParticipantsInclusion criteria included any listed diagnosis identifying poisoning by aromatic analgesics paracetamol/APAP or associated supplementary code. Generalised linear models were used to investigate the association between outcomes of inpatient admission, mortality, requirement of invasive mechanical ventilation, charges and inpatient lengths of stay based on patient, hospital and clinical characteristics.ResultsAcross the 625.2 million ED visits in the USA from 2006 to 2010, 411 811 APAP-related toxicity ED visits were observed, with 45.5% resulting in inpatient admission, 4.7% requiring invasive mechanical ventilation and 0.6% involving death. Overall, the incidence proportion was 27.10 per 100 000 US population, exceeding 70 per 100 000 at age 2 years and ages 16–18 years. The total national bill was $1.06 billion per year (US$ 2014), and predominantly involved females (65.5%) and intentional self-harm (58.4%), which were notably higher within the 12–20 years age category (female12–20 years=74.8%, intentional self-harm12–20 years=71.4%). Behavioural and mental health comorbidities were relatively common and associated with an increased relative risk of admission and likelihood of charges almost entirely across all age categories of ≥12 years within the multivariable analyses. The number of ED visits did not appreciably change over time, decreasing by <2% from 2006 to 2010 (n=1351). Multivariable results also suggested no consistent change in outcomes across the study's time horizon.ConclusionsA substantial public health impact of APAP toxicity-related cases was observed in the US from 2006 to 2010, with incidence proportions peaking at age 2 years and ages 16–18 years. After controlling for numerous factors, no consistent change was observed over the 5-year time horizon concerning outcomes of admission, mortality, invasive mechanical ventilation, charges or length of stay.
Variation in use of non-surgical treatments among osteoarthritis patients in orthopaedic practice in the Netherlands
Authors: Hofstede Stefanie N , Vliet Vlieland Thea P M , van den Ende Cornelia H M , Nelissen Rob G H H , Marang-van de Mheen Perla J , van Bodegom-Vos Leti 
Published: September 2015

ObjectivesNational and international evidence-based guidelines for hip and knee osteoarthritis (OA) recommend to start with non-surgical treatments, followed by surgical intervention if a patient does not respond sufficiently to non-surgical treatments, but there are indications that these are not optimally used. The aim of this study was to assess the extent to which all recommended non-surgical treatments were used by patients with hip or knee OA who receive(d) a total hip or knee replacement, as reported by patients and orthopaedic surgeons.SettingWe performed two cross-sectional internet-based surveys among patients and orthopaedic surgeons throughout the Netherlands.Participants195 OA patients either have undergone total knee arthroplasty or total hip arthroplasty no longer than 12 months ago or being on the waiting list for surgery with a confirmed date within 3 months and 482 orthopaedic surgeons were invited to participate.Primary and secondary outcome measuresThe use of recommended non-surgical treatments including education about OA/treatment options, lifestyle advice, dietary therapy, physical therapy, acetaminophen, NSAIDs and glucocorticoid injections.Results174 OA patients (93%) and 172 orthopaedic surgeons (36%) completed the surveys. Most recommended non-surgical treatments were given to the majority of patients (eg, 80% education about OA, 73% physical therapy, 72% acetaminophen, 80% NSAIDs). However, only 6% of patients and 10% of orthopaedic surgeons reported using a combination of all recommended treatments. Dietary therapy was used least frequently. Only 11% of overweight and 30% of obese participants reported having received dietary therapy and 28% of orthopaedic surgeons reported to prescribe dietary therapy to overweight patients.ConclusionsWhile most recommended non-surgical treatments were used frequently as single therapy, the combination is used in only a small percentage of OA patients. Especially, use of dietary therapy may be improved to help patients manage their symptoms, and potentially delay the need for joint arthroplasty.
Mortality from heart failure, acute myocardial infarction and other ischaemic heart disease in England and Oxford: a trend study of multiple-cause-coded death certification
Authors: Rahimi Kazem , Duncan Marie , Pitcher Alex , Emdin Connor A , Goldacre Michael J 
Published: September 2015

BackgroundAge-standardised death rates from acute myocardial infarction (AMI) and ischaemic heart disease (IHD) have been declining in most developed countries. However, the magnitude of such reductions and how they impact on death from heart failure are less certain. We sought to assess and compare temporal trends in mortality from heart failure, AMI and non-AMI IHD over a 30-year period in England.MethodsWe analysed death registration data for multiple-cause-coded mortality for all deaths in people aged 35 years and over in England from 1995 to 2010, population 52 million, and in a regional population (Oxford region) from 1981 to 2010, population 2.5 million, for which data on all causes of death were available.ResultsConsidering all ages and both sexes combined, during the 30-year observation period, age-standardised and sex-standardised mortality rates based on all certified causes of death declined by 60% for heart failure, 80% for AMI and 46% for non-AMI IHD. These longer term trends observed in the Oxford region were consistent with those for the whole of England from 1995 to 2010, with no evidence of a plateau in recent years. Although proportional reductions in rates differed by age and sex, even in those aged 85 years or more, there were substantial reductions in mortality rates in the all-England data set (50%, 66% and 20% for heart failure, AMI and non-AMI IHD, respectively).ConclusionsThis study shows large and sustained reductions in age-specific and sex-specific and standardised death rates from heart failure, as well as from AMI and non-AMI IHD, over a 30-year period in England.
Effects of “Media” on Innovation, Empirical Results
Authors: Shayan E. , Allotey M. , Ghotb F. 
Published: September 2015

Studies on the national development have mainly focused on politics and economics as the main determinants of development. There is no research known to us investigating the effects of media and communication on national development. Evidently, countries that are more media friendly have demonstrated more innovativeness, normally leading to significant levels of economic development. Literature shows that over 50% of the countries with high freedom of press index also have high global innovation index (GII). The aim of this research is to investigate such a relationship based on empirical data. The data on national innovation index GII is documented in GII 2013. However, due to dependency of these scores on an incomplete number of arbitrary media factors, a new GII (NGII), in absence of media effects, had to be recalculated following the exact procedure used by GII 2013. It was also required to draw, from a thorough literature search, an acceptable definition of media and its constituents, media items, as related to innovation. After a list of media indicators was concluded from the literature, different reliable sources of statistics were consulted to collect data on the media indicators of relevant countries under study. These values formed the observations on the independent variables. A linear regression model was developed and characterized between the dependent variable NGII and the selected media items for the 45 high income countries. Discussions and conclusions were made about all the data assumptions and behavior of the model to establish reliable results for further interpretations and conclusions. Results clearly show a positive relationship for the high income countries. This is a new finding that we believe will be of interest of the research community. To be able to generalize the results, the next step of the ongoing research will also cover middle income countries.
CD44 sensitivity of platelet activation, membrane scrambling and adhesion under high arterial shear rates
Authors: Alzoubi Kousi , Chatterjee Madhumita , Walker Britta , Münzer Patrick , Luo Dong , Umbach Anja T. , Elvira Bernat , Chen Hong , Voelkl Jakob , Föller Michael , Mak Tak Z. , Borst Oliver , Gawaz Meinrad , Lang Florian , Liu Guilai , Liu Guoxing 
Published: September 2015

SummaryCD44 is required for signalling of macrophage migration inhibitory factor (MIF), an anti-apoptotic pro-inflammatory cytokine. MIF is expressed and released from blood platelets, key players in the orchestration of occlusive vascular disease. Nothing is known about a role of CD44 in the regulation of platelet function. The present study thus explored whether CD44 modifies degranulation (P-selectin exposure), integrin activation, caspase activity, phosphatidylserine exposure on the platelet surface, platelet volume, Orai1 protein abundance and cytosolic Ca2+-activity ([Ca2+]i). Platelets from mice lacking CD44 (cd44-/- ) were compared to platelets from corresponding wild-type mice (cd44+/+ ). In resting platelets, P-selectin abundance, αllbβ3 inte-grin activation, caspase-3 activity and phosphatidylserine exposure were negligible in both genotypes and Orai1 protein abundance, [Ca2+]i, and volume were similar in cd44-/- and cd44+/+ platelets. Platelet degranulation and αllbβ3 integrin activation were significantly increased by thrombin (0.02 U/ml), collagen related peptide (CRP, 2 µg/ml and Ca2+-store depletion with thapsigargin (1 µM), effects more pronounced in cd44-/- than in cd44+/+ platelets. Thrombin (0.02 U/ml) increased platelet [Ca2+]i, caspase-3 activity, phosphatidylserine exposure and Orai1 surface abundance, effects again significantly stronger in cd44-/- than in cd44+/+ platelets. Thrombin further decreased forward scatter in cd44-/- and cd44+/+ platelets, an effect which tended to be again more pronounced in cd44-/- than in cd44+/+ platelets. Platelet adhesion and in vitro thrombus formation under high arterial shear rates (1,700 s-1) were significantly augmented in cd44-/- mice. In conclusion, genetic deficiency of CD44 augments activation, apoptosis and prothrombotic potential of platelets.
Polyphenol intake is associated with low-grade inflammation, using a novel data analysis from the Moli-sani study
Authors: Pounis George , Bonaccio Marialaura , Castelnuovo Augusto Di , Costanzo Simona , Curtis Amalia De , Persichillo Mariarosaria , Sieri Sabina , Donati Maria Benedetta , Cerletti Chiara , Gaetano Giovanni de , Iacoviello Licia 
Published: September 2015

SummaryThe association of polyphenol content of human diet with low-grade inflammation is not yet fully understood. It was the objective of this study to evaluate the association of flavonoid and lignan intake with frequently used and easily applicable in clinical practice low-grade inflammation biomarkers, in a novel holistic approach. A total of 5,948 women and 5,965 men (aged ≥ 35years) were analysed from the Moli-sani cohort, randomly recruited from the general population. The EPIC-FFQ was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone and lignan intakes were calculated using Eurofir eBASIS and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of diet in these nutrients. CRP levels, WBC and PLT count and granulocyte to lymphocyte ratio were conceived as low-grade inflammation biomarkers. INFLA-score was constructed summarizing synergistic effects of these biomarkers. The INFLA-score was negatively associated with PAC-score in different levels of adjustment, in both genders (for all β-coef< 0, P< 0.05). 10 units increase in PAC-score was associated with 5–8 % decrease in the likelihood of higher low-grade inflammation status (i. e. higher quartile of INFLA-score) in men and women (odds ratio [ORs] 0.92 to 0.95, p< 0.05). The total variation of INFLA-score that was explained by PAC-score was estimated to be 16.7 % in women and 9.1 % in men (%R2=16.7 and 9.1). In conclusion, polyphenol content of diet evaluated in a holistic approach was negatively associated with a score of low-grade inflammation biomarkers in a large population based study. For the first time low-grade inflammation was evaluated in a holistic way through INFLA-score and was associated with polyphenol content of diet.Supplementary Material to this article is available online at www.thrombosis-online.com.