bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptive Changes in Alphavirus mRNA Translation Allowed Colonization of Vertebrate Hosts
Authors: Ventoso Iván 
Published: July 2012

ABSTRACT

Members of the
Alphavirus
genus are arboviruses that alternate replication in mosquitoes and vertebrate hosts. In vertebrate cells, the alphavirus resists the activation of antiviral RNA-activated protein kinase (PKR) by the presence of a prominent RNA structure (downstream loop [DLP]) located in viral 26S transcripts, which allows an eIF2-independent translation initiation of these mRNAs. This article shows that DLP structure is essential for replication of Sindbis virus (SINV) in vertebrate cell lines and animals but is dispensable for replication in insect cells, where no ortholog of the vertebrate
PKR
gene has been found. Sequence comparisons and structural RNA analysis revealed the evolutionary conservation of DLP in SINV and predicted the existence of equivalent DLP structures in many members of the
Alphavirus
genus. A mutant SINV lacking the DLP structure evolved in murine cells to recover a wild-type phenotype by creating an alternative structure in the RNA that restored the translational independence for eIF2. Genetic, phylogenetic, and biochemical data presented here support an evolutionary scenario for the natural history of alphaviruses, in which the acquisition of DLP structure in their mRNAs probably allowed the colonization of vertebrate host and the consequent geographic expansion of some of these viruses worldwide.
Conformational Switch-Defective ϕX174 Internal Scaffolding Proteins Kinetically Trap Assembly Intermediates before Procapsid Formation
Authors: Gordon Emile B. , Knuff Christopher J. , Fane Bentley A. 
Published: July 2012

ABSTRACT
Conformational switching is an overarching paradigm in which to describe scaffolding protein-mediated virus assembly. However, rapid morphogenesis with small assembly subunits hinders the isolation of early morphogenetic intermediates in most model systems. Consequently, conformational switches are often defined by comparing the structures of virions, procapsids and aberrantly assembled particles. In contrast, ϕX174 morphogenesis proceeds through at least three preprocapsid intermediates, which can be biochemically isolated. This affords a detailed analysis of early morphogenesis and internal scaffolding protein function. Amino acid substitutions were generated for the six C-terminal, aromatic amino acids that mediate most coat-internal scaffolding protein contacts. The biochemical characterization of mutant assembly pathways revealed two classes of molecular defects, protein binding and conformational switching, a novel phenotype. The conformational switch mutations kinetically trapped assembly intermediates before procapsid formation. Although mutations trapped different particles, they shared common second-site suppressors located in the viral coat protein. This suggests a fluid assembly pathway, one in which the scaffolding protein induces a single, coat protein conformational switch and not a series of sequential reactions. In this model, an incomplete or improper switch would kinetically trap intermediates.
Virion-Associated Complement Regulator CD55 Is More Potent than CD46 in Mediating Resistance of Mumps Virus and Vesicular Stomatitis Virus to Neutralization
Authors: Johnson John B. , Lyles Douglas S. , Alexander-Miller Martha A. , Parks Griffith D. 
Published: July 2012

ABSTRACTEnveloped viruses can incorporate host cell membrane proteins during the budding process. Here we demonstrate that mumps virus (MuV) and vesicular stomatitis virus (VSV) assemble to include CD46 and CD55, two host cell regulators which inhibit propagation of complement pathways through distinct mechanisms. Using viruses which incorporated CD46 alone, CD55 alone, or both CD46 and CD55, we have tested the relative contribution of these regulators in resistance to complement-mediated neutralization. Virion-associated CD46 and CD55 were biologically active, with VSV showing higher levels of activity of both cofactors, which promoted factor I-mediated cleavage of C3b into iC3b as well as decay-accelerating factor (DAF) activity against the C3 convertase, than MuV. Time courses ofin vitroneutralization with normal human serum (NHS) showed that both regulators could delay neutralization, but viruses containing CD46 alone were neutralized faster and more completely than viruses containing CD55 alone. A dominant inhibitory role for CD55 was most evident for VSV, where virus containing CD55 alone was not substantially different in neutralization kinetics from virus harboring both regulators. Electron microscopy showed that VSV neutralization proceeded through virion aggregation followed by lysis, with virion-associated CD55 providing a delay in both aggregation and lysis more substantial than that conferred by CD46. Our results demonstrate the functional significance of incorporation of host cell factors during virion envelope assembly. They also define pathways of virus complement-mediated neutralization and suggest the design of more effective viral vectors.
A Myeloid Progenitor Cell Line Capable of Supporting Human Cytomegalovirus Latency and Reactivation, Resulting in Infectious Progeny
Authors: O'Connor Christine M. , Murphy Eain A. 
Published: July 2012

ABSTRACTHuman cytomegalovirus (HCMV) is a herpesvirus that establishes a lifelong, latent infection within a host. At times when the immune system is compromised, the virus undergoes a lytic reactivation producing infectious progeny. The identification and understanding of the biological mechanisms underlying HCMV latency and reactivation are not completely defined. To this end, we have developed a tractablein vitromodel system to investigate these phases of viral infection using a clonal population of myeloid progenitor cells (Kasumi-3 cells). Infection of these cells results in maintenance of the viral genome with restricted viral RNA expression that is reversed with the addition of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA, also known as PMA). Additionally, a latent viral transcript (LUNA) is expressed at times where viral lytic transcription is suppressed. Infected Kasumi-3 cells initiate production of infectious virus following TPA treatment, which requires cell-to-cell contact for efficient transfer of virus to other cell types. Importantly, lytically infected fibroblast, endothelial, or epithelial cells can transfer virus to Kasumi-3 cells, which fail to initiate lytic replication until stimulated with TPA. Finally, inflammatory cytokines, in addition to the pharmacological agent TPA, are sufficient for transcription of immediate-early (IE) genes following latent infection. Taken together, our findings argue that the Kasumi-3 cell line is a tractablein vitromodel system with which to study HCMV latency and reactivation.
Stem Cell-Derived Human Intestinal Organoids as an Infection Model for Rotaviruses
Authors: Finkbeiner Stacy R. , Zeng Xi-Lei , Utama Budi , Atmar Robert L. , Shroyer Noah F. , Estes Mary K. 
Published: July 2012

ABSTRACT
Directed differentiation of stem cell lines into intestine-like tissue called induced human intestinal organoids (iHIOs) is now possible (J. R. Spence, C. N. Mayhew, S. A. Rankin, M. F. Kuhar, J. E. Vallance, K. Tolle, E. E. Hoskins, V. V. Kalinichenko, S. I. Wells, A. M. Zorn, N. F. Shroyer, and J. M. Wells, Nature 470:105-109, 2011). We tested iHIOs as a new model to cultivate and study fecal viruses. Protocols for infection of iHIOs with a laboratory strain of rotavirus, simian SA11, were developed. Proof-of-principle analyses showed that iHIOs support replication of a gastrointestinal virus, rotavirus, on the basis of detection of nonstructural viral proteins (nonstructural protein 4 [NSP4] and NSP2) by immunofluorescence, increased levels of viral RNA by quantitative reverse transcription-PCR (qRT-PCR), and production of infectious progeny virus. iHIOs were also shown to support replication of 12/13 clinical rotavirus isolates directly from stool samples. An unexpected finding was the detection of rotavirus infection not only in the epithelial cells but also in the mesenchymal cell population of the iHIOs. This work demonstrates that iHIOs offer a promising new model to study rotaviruses and other gastrointestinal viruses.

IMPORTANCE
Gastrointestinal viral infections are a major cause of illness and death in children and adults. The ability to fully understand how viruses interact with human intestinal cells in order to cause disease has been hampered by insufficient methods for growing many gastrointestinal viruses in the laboratory. Induced human intestinal organoids (iHIOs) are a promising new model for generating intestine-like tissue. This is the first report of a study using iHIOs to cultivate any microorganism, in this case, an enteric virus. The evidence that both laboratory and clinical rotavirus isolates can replicate in iHIOs suggests that this model would be useful not only for studies of rotaviruses but also potentially of other infectious agents. Furthermore, detection of rotavirus proteins in unexpected cell types highlights the promise of this system to reveal new questions about pathogenesis that have not been previously recognized or investigated in other intestinal cell culture models.
Ethanolamine: A Signal to Commence a Host-Associated Lifestyle?
Authors: Garsin Danielle A. 
Published: July 2012

ABSTRACT

Ethanolamine (EA) is a compound prevalent in the gastrointestinal (GI) environment. The ability to catabolize this compound has been associated with important GI pathogens, including enterohemorrhagic
Escherichia coli
O157:H7 (EHEC). It has been hypothesized that the ability of EHEC to utilize EA as a source of nitrogen provides EHEC with an important competitive advantage in the gut. However, new work by Kendall et al. (mBio 3:e00050-12, 2012) suggests that the role of EA in EHEC pathogenesis may be more fundamental; EA appears to be a signal for EHEC to commence its virulence program. In this commentary, I review the previously described connections of EA to bacterial pathogenesis in the GI tract, highlight the important findings of this new study, and note areas where further research is needed to fully comprehend the connection of EA utilization to bacterial pathogenesis.
Inconsistencies in Nice Guidance for Acupuncture: Reanalysis and Discussion
Authors: Latimer Nicholas R , Bhanu Aathish Chandrika , Whitehurst David G T 
Published: July 2012

Background Acupuncture received a positive recommendation in the National Institute for Health and Clinical Excellence (NICE) clinical guideline for low back pain (LBP). However, no such recommendation was forthcoming in the NICE clinical guideline for osteoarthritis (OA). Importantly, the two guidelines adopted different treatment comparators in their economic analyses of acupuncture; in the LBP guideline ‘usual care’ was used (with no consideration of placebo/sham interventions), whereas ‘sham acupuncture’ was the comparator in the OA guideline. Objective To analyse the implications of using different control group comparators when estimating the cost-effectiveness of acupuncture therapy. Methods The NICE OA economic analysis for acupuncture was replicated using ‘usual care’ (ie, no placebo/sham component) as the treatment comparator. A ‘transfer-to-utility’ technique was used to transform Western Ontario and McMaster Osteoarthritis scores into EQ-5D utility scores to allow quality-adjusted life year (QALY) gains to be estimated. QALY estimates were combined with direct incremental cost estimates of acupuncture treatment to determine incremental cost-effectiveness ratios (ICERs). Results When ‘usual care’ was used as the treatment comparator, ICER point estimates were below £20 000 per QALY gained for each acupuncture trial analysed in the OA clinical guideline. In the original analysis, using placebo/sham acupuncture as the treatment comparator, ICERs were generally above £20 000 per QALY gained. Conclusion The treatment comparator chosen in economic evaluations of acupuncture therapy is likely to be a strong determinant of the cost-effectiveness results. Different comparators used in the OA and LBP NICE guidelines may have led to the divergent recommendations in the guidelines.
An ecological study on the geographic patterns of ischaemic heart disease in Portugal and its association with demography, economic factors and health resources distribution
Authors: Ferreira-Pinto Luís Manuel , Rocha-Gonçalves Francisco , Teixeira-Pinto Armando 
Published: July 2012

ObjectivesBeing one of the main causes of morbidity and mortality in developed countries, ischaemic heart disease's (IHD) incidence and mortality present clear differences between and within countries. Several authors already proposed possible explanations based on the demography, environmental factors, diet and level of urbanisation. This study reflects the Portuguese reality concerning IHD, by analysing the geographical distribution of hospital admissions and mortality due to this condition, in Portugal, and its association with demography, economical factors and the distribution of healthcare resources at the regional level.DesignEcological study.SettingData from all Portuguese Public Hospitals were obtained using the National Registry of Hospital Admissions, between 2000 and 2007, and data on demography, economical factors and health resources distribution were obtained from the National Institute of Statistics.ParticipantsAggregated statistics on hospital admissions and mortality were computed for 278 counties based on almost 200 000 admissions.Primary and secondary outcome measuresMortality rate; hospital admissions rate.ResultsThe geographical distribution of non-adjusted mortality and hospital admission showed an inner/coastal pattern but no North/South gradient was clear. Counties with higher economical development had significantly higher mortality and admission rates. However, healthcare resources distribution was not significantly associated with IHD hospital admission and mortality. When adjusted for age, gender, economic development and health resources distribution, there was still unexplained geographical variation both in hospital admissions and mortality rates.ConclusionA pattern in the geographic distribution of incidence and mortality of IHD was clear even after the adjustment for age and gender. Economical variables were the ones presenting the strongest association. These types of analysis may be very helpful for the definition of health policies, in particular to identify priority regions for disease prevention and guidelines for healthcare resources distribution.
Socio-demographic characteristics of women sustaining injuries during pregnancy: a study from the Danish National Birth Cohort
Authors: Virk Jasveer , Hsu Paul , Olsen Jørn 
Published: July 2012

ObjectivesTo describe adverse birth outcomes associated with hospital-treated injuries that took place among women in the Danish National Birth Cohort.DesignLongitudinal cohort study.SettingDenmark.Participants90 452 women and their offspring selected from the Danish National Birth Cohort.Primary and secondary outcome measuresTo determine if injured women were more likely to deliver an infant preterm, with low birth weight, stillborn or have a spontaneous abortion, the authors estimated HRs. ORs were generated to assess APGAR scores and infants born small for gestational age (SGA). Models were adjusted for maternal smoking and drinking during pregnancy, household socioeconomic status, eclampsia/pre-eclampsia or gestational diabetes status during pregnancy and maternal age at birth; estimates for preterm birth were also adjusted for prior history of preterm birth.ResultsIn the cohort of 90 452 pregnant women, 3561 (3.9%) received medical treatment for an injury during pregnancy. Injured pregnant women were more likely to deliver infants that were stillborn or have pregnancies terminated by spontaneous abortion. The authors did not detect an adverse effect between injuries sustained during pregnancy and delivery of preterm, low birth weight or SGA infants, or infants with an APGAR score of <7.ConclusionsThe study shows that injuries occurring among women from an unselected population may not have an adverse effect on birth weight, gestational age, APGAR score or SGA status but may adversely affect the risk of stillbirth and spontaneous abortions in some situations.
Differential use of extended and immediate release quetiapine: a retrospective registry study of Finnish inpatients with schizophrenia spectrum and bipolar disorders
Authors: Hallinen Taru , Soini Erkki J , Granström Ola , Ovaskainen Yrjö , Leinonen Esa , Koponen Hannu J , Hänninen Kari 
Published: July 2012

ObjectiveExtended release (XR) and immediate release (IR) quetiapine have differing dosing, titration and plasma concentration profiles. The authors assessed whether the use of quetiapine XR and IR in schizophrenia spectrum disorders (SCZ) and bipolar disorder (BD) differ.DesignRetrospective non-interventional registry study.SettingSecondary healthcare.ParticipantsAll SCZ and BD (ICD-10 codes F20–F29, F30–F31) patients discharged between June 2008 and June 2010 from a Finnish psychiatric hospital with any use of quetiapine during their inpatient stay.Primary and secondary outcome measuresDifferences in patient characteristics between quetiapine XR and IR users were tested. To assess the profile of XR versus IR patients, logistic regressions were performed.Results43 patients used quetiapine XR, 58 used quetiapine IR and 55 used both formulations (n=156). 102 patients were diagnosed with SCZ and 54 with BD, with no significant differences between the quetiapine formulations. The mean daily dose of quetiapine XR was significantly higher than that of quetiapine IR (542 mg vs 328 mg; p<0.001). This was also true for the SCZ subgroup (XR: 593 mg vs IR: 338 mg; p<0.001) and the BD subgroup (XR: 466 mg vs IR: 308 mg; p=0.009). 48% of all quetiapine IR patients used a mean dose of ≤200 mg compared with 2% of XR patients. Injectable antipsychotics were combined with quetiapine IR but not with quetiapine XR (12% vs 0%; p=0.019). At discharge, quetiapine XR was used as monotherapy to a greater extent than IR (79% vs 44%; p=0.003). The odds for quetiapine XR use in hospital were lower with advancing age, substance abuse diagnosis and prior IR use.ConclusionsAmong SCZ and BD inpatients, quetiapine XR was more often used as monotherapy and in significantly higher doses than quetiapine IR. Differential use of the quetiapine formulations appears to depend, at least in part, on patient characteristics.
Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study
Authors: Roetker Nicholas S , Yonker James A , Lee Chee , Chang Vicky , Basson Jacob J , Roan Carol L , Hauser Taissa S , Hauser Robert M , Atwood Craig S 
Published: July 2012

ObjectivesSingle genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene–gene (G × G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression.DesignA retrospective cohort study.SettingA survey of participants in the Wisconsin Longitudinal Study.ParticipantsA total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white.Primary outcome measureDepression as determine by the Composite International Diagnostic Interview–Short-Form.ResultsUsing a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G × G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1rs1800497 (also known asDRD2Taq1A) in men andDRD2rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTOrs1421085 in women, p=0.008). However, after controlling for G × G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men:GNRH1novel SNP: (1.43 → 1.57); women:APOC3rs2854116: (1.28 → 1.55),ACVR2Brs3749386: (1.11 → 2.17),FTOrs1421085: (1.32 → 1.65),IL6rs1800795: (1.12 → 1.85)).ConclusionsThe results suggest that examining G × G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1andDRD2) and neuroendocrine (GNRH1andACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology.
Increase in self-reported migraine prevalence in the Danish adult population: a prospective longitudinal population-based study
Authors: Le Han , Tfelt-Hansen Peer , Skytthe Axel , Kyvik Kirsten Ohm , Olesen Jes 
Published: July 2012

ObjectiveIt is uncertain whether migraine prevalence has increased in modern society. The aim of this study was to assess any change in migraine prevalence over an 8-year period among the adult population in Denmark.DesignProspective longitudinal population-based study.Setting30 000 twin individuals were invited to participate in two cross-sectional questionnaire surveys containing validated questions to diagnose migraine in 1994 and 2002. The twins are representative of the Danish population with regard to migraine and other somatic diseases.ParticipantsThe 1994 cohort comprised 28 571 twin individuals aged 12–41 years and the 2002 cohort 31 865 twin individuals aged 20–71 years.Outcome measuresSex-, age- and subtype-specific incidence and lifetime prevalence as well as 1-year prevalence of migraine.Results1-year prevalence in 2002 was 12.3% for migraine, 4.1% for migraine with aura and 8.2% for migraine without aura. Lifetime prevalence of migraine was 16.1% in 1994 (aged 12–41 years) and 25.2% in 2002 (aged 20–71 years). Lifetime prevalence of migraine for age 20–41 was increased from 1994 to 2002 (18.5% vs 24.5%) by 32.2% (95% CI 27.0% to 37.3%; p<0.001). The difference was primarily seen in the population older than 32 years. The increase was especially evident in migraine with aura (5.6% vs 9.4%, p<0.001) but also a significant increase in migraine without aura was found (13.0% vs 15.1%, p<0.001). Eight-year period incidence rate of migraine was 0.141 corresponding to an average annual incidence rate of 17.6 per 1000 person-years.ConclusionsLifetime prevalence of migraine in Denmark increased substantially from 1994 to 2002. Part of the increase may be due to increased medical consultation resulting in increased rate of physician diagnosis or awareness due to previously participation in the 1994 survey. It is pertinent to study the environmental causes of the increase and to implement preventive measures.