bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of Serine Codon Conservation Reveals Diverse Phenotypic Constraints on Hepatitis C Virus Glycoprotein Evolution
Authors: Brown Richard J. P. , Koutsoudakis George , Urbanowicz Richard A. , Mirza Deeman , Ginkel Corinne , Riebesehl Nina , Calland Noémie , Albecka Anna , Price Louisa , Hudson Natalia , Descamps Véronique , Backx Matthijs , McClure C. Patrick , Duverlie Gilles , Pecheur Eve-Isabelle , Dubuisson Jean , Perez-del-Pulgar Sofia , Forns Xavier , Steinmann Eike , Tarr Alexander W. , Pietschmann Thomas , Ball Jonathan K. 
Published: October 2013

ABSTRACT

Serine is encoded by two divergent codon types, UCN and AGY, which are not interchangeable by a single nucleotide substitution. Switching between codon types therefore occurs via intermediates (threonine or cysteine) or via simultaneous tandem substitutions. Hepatitis C virus (HCV) chronically infects 2 to 3% of the global population. The highly variable glycoproteins E1 and E2 decorate the surface of the viral envelope, facilitate cellular entry, and are targets for host immunity. Comparative sequence analysis of globally sampled
E1E2
genes, coupled with phylogenetic analysis, reveals the signatures of multiple archaic codon-switching events at seven highly conserved serine residues. Limited detection of intermediate phenotypes indicates that associated fitness costs restrict their fixation in divergent HCV lineages. Mutational pathways underlying codon switching were probed via reverse genetics, assessing glycoprotein functionality using multiple
in vitro
systems. These data demonstrate selection against intermediate phenotypes can act at the structural/functional level, with some intermediates displaying impaired virion assembly and/or decreased capacity for target cell entry. These effects act in residue/isolate-specific manner. Selection against intermediates is also provided by humoral targeting, with some intermediates exhibiting increased epitope exposure and enhanced neutralization sensitivity, despite maintaining a capacity for target cell entry. Thus, purifying selection against intermediates limits their frequencies in globally sampled strains, with divergent functional constraints at the protein level restricting the fixation of deleterious mutations. Overall our study provides an experimental framework for identification of barriers limiting viral substitutional evolution and indicates that serine codon-switching represents a genomic “fossil record” of historical purifying selection against E1E2 intermediate phenotypes.
Immunosuppression Facilitates the Reactivation of Latent Papillomavirus Infections
Authors: Maglennon G. A. , McIntosh P. B. , Doorbar J. 
Published: October 2013

ABSTRACT
At mucosal sites, papillomavirus genomes can persist in the epithelial basal layer following immune-mediated regression. Subsequent T-cell depletion stimulates a 3- to 5-log increase in the viral copy number, to levels associated with productive infection. Reappearance of microlesions was rare within the short time frame of our experiments but was observed in one instance. Our studies provide direct evidence that immunosuppression can trigger the reactivation of latent papillomavirus genomes, as previously proposed in humans.
Type I Interferon Limits the Capacity of Bluetongue Virus To Infect Hematopoietic Precursors and Dendritic Cells
In Vitro
and
In Vivo
Authors: Rodríguez-Calvo Teresa , Rojas José-Manuel , Martín Verónica , Sevilla Noemí 
Published: October 2013

ABSTRACT

Hematopoietic stem cells (HSCs) give rise to progenitors with potential to produce multiple cell types, including dendritic cells (DCs). DCs are the principal antigen-presenting cells and represent the crucial link between innate and adaptive immune responses. Bluetongue virus (BTV), an economically important
Orbivirus
of the
Reoviridae
family, causes a hemorrhagic disease mainly in sheep and occasionally in other species of ruminants. BTV is transmitted between its mammalian hosts by certain species of biting midges (
Culicoides
spp.) and is a potent alpha interferon (IFN-α) inducer. In the present report, we show that BTV infects cells of hematopoietic origin but not HSCs in immunocompetent sheep. However, BTV infects HSCs in the absence of type I IFN (IFN-I) signaling
in vitro
and
in vivo
. Infection of HSCs
in vitro
results in cellular death by apoptosis. Furthermore, BTV infects bone marrow-derived DCs (BM-DCs), interfering with their development to mature DCs in the absence of type I IFN signaling. Costimulatory molecules CD80 and CD86 and costimulatory molecules CD40 and major histocompatibility complex class II (MHC-II) are affected by BTV infection, suggesting that BTV interferes with DC antigen-presenting capacity.
In vivo
, different DC populations are also affected during the course of infection, probably as a result of a direct effect of BTV replication in DCs and the production of infectious virus. These new findings suggest that BTV infection of HSCs and DCs can impair the immune response, leading to persistence or animal death, and that this relies on IFN-I.
Herpes Simplex Virus 1 Protein Kinase Us3 Phosphorylates Viral dUTPase and Regulates Its Catalytic Activity in Infected Cells
Authors: Kato Akihisa , Tsuda Shumpei , Liu Zhuoming , Kozuka-Hata Hiroko , Oyama Masaaki , Kawaguchi Yasushi 
Published: October 2013

ABSTRACT

Us3 is a serine-threonine protein kinase encoded by herpes simplex virus 1 (HSV-1). In this study, a large-scale phosphoproteomic analysis of titanium dioxide affinity chromatography-enriched phosphopeptides from HSV-1-infected cells using high-accuracy mass spectrometry (MS) and subsequent analyses showed that Us3 phosphorylated HSV-1-encoded dUTPase (vdUTPase) at serine 187 (Ser-187) in HSV-1-infected cells. Thus, the following observations were made. (i) In
in vitro
kinase assays, Ser-187 in the vdUTPase domain was specifically phosphorylated by Us3. (ii) Phosphorylation of vdUTPase Ser-187 in HSV-1-infected cells was detected by phosphate-affinity polyacrylamide gel electrophoresis analyses and was dependent on the kinase activity of Us3. (iii) Replacement of Ser-187 with alanine (S187A) in vdUTPase and an amino acid substitution in Us3 that inactivated its kinase activity significantly downregulated the enzymatic activity of vdUTPase in HSV-1-infected cells, whereas a phosphomimetic substitution at vdUTPase Ser-187 restored the wild-type enzymatic activity of vdUTPase. (iv) The vdUTPase S187A mutation as well as the kinase-dead mutation in Us3 significantly reduced HSV-1 replication in human neuroblastoma SK-N-SH cells at a multiplicity of infection (MOI) of 5 but not at an MOI of 0.01, whereas the phosphomimetic substitution at vdUTPase Ser-187 restored the wild-type viral replication at an MOI of 5. In contrast, these mutations had no effect on HSV-1 replication in Vero and HEp-2 cells. Collectively, our results suggested that Us3 phosphorylation of vdUTPase Ser-187 promoted HSV-1 replication in a manner dependent on cell types and MOIs by regulating optimal enzymatic activity of vdUTPase.
Characterization of Blockade Antibody Responses in GII.2.1976 Snow Mountain Virus-Infected Subjects
Authors: Swanstrom Jesica , Lindesmith Lisa C. , Donaldson Eric F. , Yount Boyd , Baric Ralph S. 
Published: October 2013

ABSTRACT
Snow Mountain virus (GII.2.1976) is the prototype strain of GII.2 noroviruses (NoVs), which cause an estimated 8% of norovirus outbreaks, yet little is known about the immunobiology of these viruses. To define the human immune response induced by SMV infection and the antigenic relationship between different GII.2 strains that have circulated between 1976 and 2010, we developed a panel of four GII.2 variant virus-like particles (VLPs) and compared their antigenicities by enzyme immunoassay (EIA) and surrogate antibody neutralization (blockade) assays. Volunteers infected with GII.2.1976 developed a mean 167-fold increase in blockade response against the homotypic VLP by day 8 postchallenge. Blockade extended cross-genotype activity in some individuals but not cross-genogroup activity. Polyclonal sera from GII.2.1976-infected volunteers blocked GII.2.1976 significantly better than they blocked GII.2.2002, GII.2.2008, and GII.2.2010, suggesting that blockade epitopes within the GII.2 strains have evolved in the past decade. To potentially map these epitope changes, we developed mouse monoclonal antibodies (MAbs) against GII.2.1976 VLPs and compared their reactivities to a panel of norovirus VLPs. One MAb had broad cross-genogroup EIA reactivity to a nonblockade, linear, conserved epitope. Six MAbs recognized conformational epitopes exclusive to the GII.2 strains. Two MAbs recognized GII.2 blockade epitopes, and both blocked the entire panel of GII.2 variants. These data indicate that the GII.2 strains, unlike the predominant GII.4 strains, have undergone only a limited amount of evolution in blockade epitopes between 1976 and 2010 and indicate that the GII.2-protective component of a multivalent norovirus vaccine may not require frequent reformulation.
Is there a relationship between subacromial impingement syndrome and scapular orientation? A systematic review
Authors: Ratcliffe Elizabeth , Pickering Sharon , McLean Sionnadh , Lewis Jeremy 
Published: October 2013

BackgroundAlterations in scapular orientation and dynamic control, specifically involving increased anterior tilt and downward rotation, are considered to play a substantial role in contributing to a subacromial impingement syndrome (SIS). Non-surgical intervention aims at restoring normal scapular posture. The research evidence supporting this practice is equivocal.ObjectiveThe aim of this study was to systematically review the relevant literature to examine whether a difference exists in scapular orientation between people without shoulder symptoms and those with SIS.Data sourcesMEDLINE, AMED, EMBASE, CINAHL, PEDro and SPORTDiscus databases were searched using relevant search terms up to August 2013. Additional studies were identified by hand-searching the reference lists of pertinent articles.Review methodsOf the 7445 abstracts identified, 18 were selected for further analysis. Two reviewers independently assessed the studies for inclusion, data extraction and quality, using a modified Downs and Black quality assessment tool.Results10 trials were included in the review. Scapular position was determined through two-dimensional radiological measurements, 360° inclinometers and three-dimensional motion and tracking devices. The findings were inconsistent. Some studies reported patterns of reduced upward rotation, increased anterior tilting and medial rotation of the scapula. In contrast, others reported the opposite, and some identified no difference in motion when compared to asymptomatic controls.ConclusionsThe underlying aetiology of SIS is still debated. The results of this review demonstrated a lack of consistency of study methodologies and results. Currently, there is insufficient evidence to support a clinical belief that the scapula adopts a common and consistent posture in SIS. This may reflect the complex, multifactorial nature of the syndrome. Additionally, it may be due to the methodological variations and shortfalls in the available research. It also raises the possibility that deviation from a ‘normal’ scapular position may not be contributory to SIS but part of normal variations. Further research is required to establish whether a common pattern exists in scapular kinematics in SIS patients or whether subgroups of patients with common patterns can be identified to guide management options. Non-surgical treatment involving rehabilitation of the scapula to an idealised normal posture is currently not supported by the available literature.
Higher psychological distress is associated with unintentional injuries in US adults
Authors: McAninch Jana , Greene Christina , Sorkin John D , Lavoie Marie-Claude , Smith Gordon S 
Published: October 2013

BackgroundLinks between mental illness, self-inflicted injury and interpersonal violence are well recognised, but the association between poor mental health and unintentional injuries is not well understood.MethodsWe used the 2010 National Health Interview Survey to assess the association between psychological distress and unintentional non-occupational injuries among US adults. Psychological distress was measured by the Kessler Psychological Distress Scale, a symptom scale shown to identify community-dwelling persons with mental illness. Multivariable logistic regression was used to estimate adjusted ORs (AOR) and 95% CIs.ResultsOf the 26 776 individuals analysed, 2.5% reported a medically attended unintentional injury in the past 3 months. Those with moderate and severe psychological distress had 1.5 (1.2 to 1.8) and 2.0 (1.4 to 2.8) times higher odds of injury, respectively, as compared to those with low distress levels, after adjusting for age, sex, race, marital status, education level, alcohol use, physical functional limitation, medical comorbidity, employment status and health insurance status. Psychological distress was significantly associated with falls (AOR 1.4 (1.1 to 1.9)) and sprain/strain injuries (AOR 2.0 (1.5 to 2.8)), but not transportation-related injuries (AOR 1.2 (0.7 to 1.9)) or fractures (AOR 1.1 (0.8 to 1.6)).ConclusionsAmong community-dwelling US adults, psychological distress is significantly associated with unintentional non-occupational injury, and the magnitude of association increases with severity of distress. The association between psychological distress and injury may be particularly strong for falls and sprain/strain injuries. These findings draw attention to a large group of at-risk individuals that may merit further targeted research, including longitudinal studies.
Vasa Vasorum Enhancement on Computerized Tomographic Angiography Correlates With Symptomatic Patients With 50% to 70% Carotid Artery Stenosis
Authors: Romero Javier M. , Pizzolato Raffaella , Atkinson Wendy , Meader Anna , Jaimes Camilo , Lamuraglia Glenn , Jaff Michael R. , Buonanno Ferdinando , Almandoz Josser Delgado , Gonzalez Ramon G. 
Published: October 2013

Background and Purpose—
Significant stenosis of the internal carotid artery (ICA) is an established stroke risk factor. Recent evidence suggests that features within the atherosclerotic plaque also have prognostic value. The purpose of this study was to correlate the enhancement of the vasa vasorum (VV) overlying the carotid artery plaque with acute neurological symptoms in patients with 50% to 70% ICA stenosis.

Methods—
We conducted a 4-year retrospective computerized tomographic angiographic review to identify patients with 50% to 70% stenosis of the ICA. Three types of plaques were identified: enhancing VV, calcified, and nonenhancing-noncalcified. Medical records were reviewed for cardiovascular risk factors and neurological status, and imaging was reviewed for signs of a recent stroke.

Results—

We identified a total of 428 patients with 50% to 70% ICA stenosis: 103 (24.1%) had enhancing VV, 202 (47.2%) calcified, and 123 (28.7%) nonenhancing-noncalcified arteries; 97 were symptomatic and 331 asymptomatic. Thirty-three (34%) symptomatic subjects demonstrated enhancing VV, 42 (20%) had calcified arterial plaques, and 22 (17%) had nonenhancing-noncalcified arterial plaques. Fisher exact tests revealed that the proportion of symptomatic individuals with enhancing VV plaque was double that of the other groups combined (
P
=0.015; odds ratio, 1.92; 95% confidence interval, 1.17–3.16). Regression analyses confirmed this association as independent from other known cardiovascular risk factors.

Conclusions—
In patients with 50% to 70% ICA stenosis, VV enhancement recognized on computed tomographic angiography is strongly associated with acute neurological symptoms compared with calcified and nonenhancing-noncalcified arterial plaques. This finding may aid in the identification of patients at increased risk for ischemic stroke within populations with the same degree of stenosis.
The Movement of Popular and Neighborhood Assemblies in the City of Buenos Aires, 2002–2011
Authors: Mauro Sebastián , Rossi Federico M. 
Published: October 2013

The assembly movement of Buenos Aires was one of the main political actors that emerged with the social explosion of December 2001. It initially called for a complete renewal of the country’s elites, but it gradually divided into a sector that focused on neighborhood demands and a sector that adopted a national perspective. A detailed examination of a decade of development of two assemblies that are paradigmatic examples of the movement’s division show that they retained their political identities over time, with the result that the “neighborhood” assembly disbanded once the problems on which it had concentrated were considered resolved while the “popular” assembly continued to engage in cultural and political projects. El movimiento asambleario de Buenos Aires fue uno de los más importantes actores políticos que emergió con la explosión social de diciembre de 2001. Inicialmente reclamaba la completa renovación de las elites, pero gradualmente fue dividiéndose en un sector que se enfocó en demandas barriales y otro sector que adoptó una perspectiva nacional. Un examen detallado de una década de desarrollo de dos asambleas que son consideradas ejemplos paradigmáticos de la división del movimiento muestra que ambas asambleas conservaron a través del tiempo sus identidades, con el resultado de que la asamblea “vecinal” se disolvió una vez que consideraron resueltos los problemas en los que se enfocaba, mientras que la asamblea “popular” continuó activamente involucrada en proyectos políticos y culturales.
Medial Reefing Without Lateral Release for Recurrent Patellar Instability
Authors: Boddula Madhav R. , Adamson Gregory J. , Pink Marilyn M. 
Published: October 2013

Background: There is no consensus on the optimal surgical technique for recurrent patellofemoral instability. Despite many different surgical procedures discussed in the literature, there are few studies with long-term outcomes. Hypothesis/Purpose: The purpose of this study was to compare subjective and objective preoperative data from patients with recurrent patellar instability and normal alignment to midterm and long-term outcomes after an arthroscopically assisted medial reefing technique. The hypothesis was that the previously reported successful outcomes at 60 months would be well maintained over time. Study Design: Case series; Level of evidence, 4. Methods: A total of 19 patients (20 knees) with recurrent patellar instability and normal bony anatomy underwent arthroscopically assisted medial reefing without lateral release. They were evaluated preoperatively and then at midterm (average, 63 months) and long-term (average, 142 months) follow-ups. Patients underwent a history assessment, physical examination, and radiographic evaluation. Outcomes evaluated included Lysholm and Tegner scores, subjective data, and examination and radiographic findings. Operative reports were reviewed for the presence of chondral lesions. Comparative statistics were utilized ( P < .05). Results: All patients were satisfied with their surgery results and would undergo the procedure again. There was 1 recurrent subluxation and no recurrent dislocations. Subjective symptom scores demonstrated significant improvement from preoperative to midterm and long-term follow-ups for pain, instability, and swelling. Both Lysholm and Tegner scores improved significantly from preoperative to midterm and long-term follow-ups. At long-term follow-up, 70% of the patients reported excellent or good results, 5 patients reported fair results, and 1 patient reported a poor result. However, Tegner activity scores decreased significantly from midterm to long-term follow-ups. Significant improvement from preoperative to midterm and long-term follow-ups was demonstrated in physical examination findings including decreases in patellar apprehension and patellar quadrant glide; however, there was no significant difference in retropatellar pain or range of motion. For radiographic measurements, the lateral patellofemoral angle was significantly improved from preoperative to midterm and long-term follow-ups. At long-term radiographic analysis, 5 knees (25%) had narrowing of the patellofemoral joint space, 10 knees (50%) revealed patellofemoral osteophytes, and 7 knees (35%) demonstrated a medial ossicle. The presence of preoperative chondral lesions resulted in significantly lower Lysholm and Tegner scores and increased findings of osteoarthritis at long-term follow-up. Conclusion: Arthroscopically assisted medial reefing, without lateral release, is an effective long-term treatment for patients with recurrent patellar instability and normal bony anatomy.
Potential association of pulmonary tuberculosis with genetic polymorphisms of toll-like receptor 9 and interferon-gamma in a Chinese population
Authors: Yang Yu , Li Xiangwei , Cui Wei , Guan Ling , Shen Fei , Xu Jinsheng , Zhou Feng , Li Mufei , Gao Cong , Jin Qi , Liu Jianmin , Gao Lei 
Published: October 2013

Abstract

Background
Association studies have been employed to investigate the relationships between host single nucleotide polymorphisms (SNPs) and susceptibility to pulmonary Tuberculosis (PTB). However, such candidate genetic markers have not been widely studied in Chinese population, especially with respect to the disease development from latent M. tuberculosis infection (LTBI).

Methods
In this case–control study, 44 candidate SNPs were examined in a total of 600 participants (PTB patients, LTBI controls and healthy controls without M. tuberculosis infection) from Zhengzhou, China. The two groups of controls were frequency matched on gender and age with PTB patients. Genotyping was carried out by the Illumina Golden Gate assay.

Results
When comparing PTB patients with LTBI controls but not healthy controls without M. tuberculosis infection, significant associations with disease development were observed for TLR9 1174 A/G, TLR9 1635 A/G and IFNG 2109G/A. The two loci in TLR9 were in LD in our study population (r2=0.96, D’=1.00). A combined effect of the genotypes associated with increased risk of PTB (i.e. TLR9 1174G/G and IFNG 2109 A/A) was found when comparing PTB patients with LTBI controls (p=0.004) but not with healthy controls without infection (p=0.433).

Conclusions
Potential associations between TLR9 and IFN-γ genetic polymorphisms and PTB were observed in a Chinese population which supports further study of the roles played by TLR9/IFN-γ pathway during the development of PTB.