bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T Cells Prevent Th2 Immune Responses and Pulmonary Eosinophilia during Respiratory Syncytial Virus Infection in Mice
Authors: Durant Lydia R. , Makris Spyridon , Voorburg Cornelia Maaike , Loebbermann Jens , Johansson Cecilia , Openshaw Peter J. M. 
Published: August 2013

ABSTRACT

During viral infection, inflammation and recovery are tightly controlled by competing proinflammatory and regulatory immune pathways. Respiratory syncytial virus (RSV) is the leading global cause of infantile bronchiolitis, which is associated with recurrent wheeze and asthma diagnosis in later life. Th2-driven disease has been well described under some conditions for RSV-infected mice. In the present studies, we used the
Foxp3
DTR
mice (which allow specific conditional depletion of Foxp3
+
T cells) to investigate the functional effects of regulatory T cells (Tregs) during A2-strain RSV infection. Infected Treg-depleted mice lost significantly more weight than wild-type mice, indicating enhanced disease. This enhancement was characterized by increased cellularity in the bronchoalveolar lavage (BAL) fluid and notable lung eosinophilia not seen in control mice. This was accompanied by abundant CD4
+
and CD8
+
T cells exhibiting an activated phenotype and induction of interleukin 13 (IL-13)- and GATA3-expressing Th2-type CD4
+
T cells that remained present in the airways even 14 days after infection. Therefore, Treg cells perform vital anti-inflammatory functions during RSV infection, suppressing pathogenic T cell responses and inhibiting lung eosinophilia. These findings provide additional evidence that dysregulation of normal immune responses to viral infection may contribute to severe RSV disease.
Morphogenesis of Mimivirus and Its Viral Factories: an Atomic Force Microscopy Study of Infected Cells
Authors: Kuznetsov Yuri G. , Klose Thomas , Rossmann Michael , McPherson Alexander 
Published: August 2013

ABSTRACT
Amoebas infected with mimivirus were disrupted at sequential stages of virus production and were visualized by atomic force microscopy. The development of virus factories proceeded over 3 to 4 h postinfection and resulted from the coalescence of 0.5- to 2-μm vesicles, possibly bearing nucleic acid, derived from either the nuclear membrane or the closely associated rough endoplasmic reticulum. Virus factories actively producing virus capsids on their surfaces were imaged, and this allowed the morphogenesis of the capsids to be delineated. The first feature to appear on a virus factory surface when a new capsid is born is the center of a stargate, which is a pentameric protein oligomer. As the arms of the stargate grow from the pentamer, a rough disk the diameter of a capsid thickens around it. This marks the initial emergence of a protein-coated membrane vesicle. The capsid self-assembles on the vesicle. Hillocks capped by different pentameric proteins spontaneously appear on the emerging vesicle at positions that are ultimately occupied by 5-fold icosahedral vertices. A lattice of coat protein nucleates at each of the 5-fold vertices, but not at the stargate, and then spreads outward from the vertices over the surface, merging seamlessly to complete the icosahedral capsid. Filling with DNA and associated proteins occurs by the transfer of nucleic acid from the interior of the virus factory into the nearly completed capsids. The portal, through which the DNA enters, is sealed by a plug of protein having a diameter of about 40 nm. A layer of integument protein that anchors the surface fibers is acquired by the passage of capsids through a membrane enriched in the protein. The coating of surface fibers is similarly acquired when the integument protein-coated capsids pass through a second membrane that has a forest of surface fibers embedded on one side.
Divergent MicroRNA Targetomes of Closely Related Circulating Strains of a Polyomavirus
Authors: Chen Chun Jung , Cox Jennifer E. , Kincaid Rodney P. , Martinez Angel , Sullivan Christopher S. 
Published: August 2013

ABSTRACT
Hundreds of virus-encoded microRNAs (miRNAs) have been uncovered, but an in-depth functional understanding is lacking for most. A major challenge for the field is separating those miRNA targets that are biologically relevant from those that are not advantageous to the virus. Here, we show that miRNAs from related variants of the polyomavirus simian vacuolating virus 40 (SV40) have differing host target repertoires (targetomes) while their direct autoregulatory activity on virus-encoded early gene products is completely preserved. These results underscore the importance of miRNA-mediated viral gene autoregulation in some polyomavirus life cycles. More broadly, these findings imply that some host targets of virus-encoded miRNAs are likely to be of little selective advantage to the virus, and our approach provides a strategy for prioritizing relevant targets.
Bovine Herpesvirus 1 Regulatory Proteins bICP0 and VP16 Are Readily Detected in Trigeminal Ganglionic Neurons Expressing the Glucocorticoid Receptor during the Early Stages of Reactivation from Latency
Authors: Frizzo da Silva Leticia , Kook Insun , Doster Alan , Jones Clinton 
Published: August 2013

ABSTRACTBovine herpesvirus 1 (BHV-1) establishes a lifelong latent infection in sensory neurons following acute infection. Increased corticosteroid levels, due to stress, increases the incidence of reactivation from latency. Within minutes, corticosteroids activate the glucocorticoid receptor and transcription of promoters containing a glucocorticoid receptor element. A single intravenous injection of the synthetic corticosteroid dexamethasone consistently induces reactivation from latency in calves. Lytic cycle viral gene expression is detected within 6 h after dexamethasone treatment of calves latently infected with BHV-1. Cellular transcription factors are induced by dexamethasone in trigeminal ganglionic neurons within 1.5 h after dexamethasone treatment, suggesting they promote viral gene expression during the early phases of reactivation from latency, which we operationally defined as the escape from latency. In this study, immunohistochemistry was utilized to examine viral protein expression during the escape from latency. Within 1.5 h after dexamethasone treatment, bICP0 and a late protein (VP16) were consistently detected in a subset of trigeminal ganglionic neurons. Most neurons expressing bICP0 also expressed VP16. Additional studies revealed that neurons expressing the glucocorticoid receptor also expressed bICP0 or VP16 at 1.5 h after dexamethasone treatment. Two other late proteins, glycoprotein C and D, were not detected until 6 h after dexamethasone treatment and were detected in only a few neurons. These studies provide evidence that VP16 and the promiscuous viraltrans-activator (bICP0) are expressed during the escape from latency, suggesting they promote the production of infectious virus in a small subset of latently infected neurons.
Rotavirus NSP4 Triggers Secretion of Proinflammatory Cytokines from Macrophages via Toll-Like Receptor 2
Authors: Ge Yi , Mansell Ashley , Ussher James E. , Brooks Anna E. S. , Manning Kristy , Wang Carol J. H. , Taylor John A. 
Published: August 2013

ABSTRACT

Nonstructural protein 4 (NSP4), encoded by rotavirus, exhibits various properties linked to viral pathogenesis, including enterotoxic activity. A recent study (O. V. Kavanagh et al., Vaccine 28:3106-3111, 2010) indicated that NSP4 also has adjuvant properties, suggesting a possible role in the innate immune response to rotavirus infection. We report here that NSP4 purified from the medium of rotavirus-infected Caco-2 cells triggers the secretion of proinflammatory cytokines from macrophage-like THP-1 cells and nitric oxide from murine RAW 264.7 cells. Secretion is accompanied by the stimulation of p38 and JNK mitogen-activated protein kinases (MAPKs) and nuclear factor NF-κB. NSP4 triggered the secretion of cytokines from murine macrophages derived from wild-type but not MyD88
−/−
or Toll-like receptor 2 (TLR2
−/−
) mice and induced secretion of interleukin-8 (IL-8) from human embryonic kidney cells transfected with TLR2 but not TLR4. Our studies identify NSP4 as a pathogen-associated molecular pattern (PAMP) encoded by rotavirus and provide a mechanism for the production of proinflammatory cytokines associated with the clinical symptoms of infection in humans and animals.
Evaluating the reproductive performance of British beef and dairy herds using national cattle movement records
Authors: Gates M. C. 
Published: August 2013

National cattle movement databases provide a valuable opportunity to monitor the reproductive performance of breeding cattle on an industry‐wide scale. In this analysis, records from the Cattle Tracing System database were used to derive key measures of reproductive efficiency for British beef and dairy herds, including calving spread, age at first calving, calving interval, culling rate and calf mortality rate. At the animal level, only 8.5 per cent of beef heifers and 6.9 per cent of dairy heifers calved by the target age of 24 months. The average calving interval was 394 days for beef dams (median: 371) and 426 days for dairy dams (median: 400). Differences in performance were noted between cattle breeds. An estimated 43.9 per cent calves born in dairy herds were crossbreed beef animals, which may limit the availability of replacement dairy heifers. At the herd level, calving spread and calf mortality rates increased with herd size, while average age at first calving, calving interval, and crossbreeding generally decreased with herd size. Dam age, calving month, breed and twinning were significant risk factors for culling and calf mortality at the animal level. Wide variation in performance between individual herds highlights the potential for improving the efficiency of British cattle production.
Magma sources and tectonic setting of Central Andean andesites (25.5–28°S) related to crustal thickening, forearc subduction erosion and delamination
Authors: Kay Suzanne Mahlburg , Mpodozis Constantino , Gardeweg Moyra 
Published: August 2013

Abstract

The Central Andean margin, where the name andesite originated, is the type locality for arc andesites erupted through thick continental crust. The <25 Ma mid to high K
2
O andesites erupted from 25.5°S to 28.2°S exhibit a large variation in trace element and isotopic ratios, reflecting formation over an evolving slab, a crust thickening to 65–75 km and a frontal arc that migrated
c.
45 km eastward at 8–3 Ma. Andesites at 28–26.8°S have the most variable and extreme heavy rare earth element (REE), high field strength element (HFSE) and Ba/La ratios and wt% Na
2
O, with the highest values in those erupted as the frontal arc migrated and the slab shallowed to the south. The required garnet-bearing, feldspar-free residue is generated in both the thick crust and the mantle wedge, into which crust was injected in a peak of forearc subduction erosion as the arc migrated. Andesites at 25.5–26.8°S, east of the Puna plateau under which the slab shallowed at 18–7 Ma and then steepened as lithospheric delamination occurred, generally lack extreme REE and HFSE ratios. Their upper crust-like features reflect eruption in a mixed stress regime and incorporation of westward-flowing radiogenic crust from a region of extensive deep crustal melting to the east.
Surface-based reservoir modelling for flow simulation
Authors: Jackson M. D. , Hampson G. J. , Saunders J. H. , El-Sheikh A. , Graham G. H. , Massart B. Y. G. 
Published: August 2013

Abstract
We present a surface-based approach to reservoir model construction in which all geological heterogeneity, whether structural, stratigraphic, sedimentological or diagenetic, that impacts on the spatial distribution of petrophysical properties is modelled as one or more discrete volumes bounded by surfaces. The modelled surfaces can be deterministically interpolated between control lines or points, or incorporate a stochastic element where control data are sparse. Models constructed from surfaces are not constrained by an underlying grid; indeed, the model is generated without reference to a grid. The only difference between ‘geological’ and ‘simulation’ models is that the latter incorporates a grid or mesh to allow numerical solution of the governing flow equations, the architecture of which is driven by the architecture of the modelled surfaces. This approach to gridding (or meshing) is directly compatible with the next generation of unstructured-mesh simulators, and allows the capabilities of the latter to be utilized fully in the modelling of complex reservoir architectures. A surface-based approach to model construction may facilitate a step change in reservoir modelling capabilities: once the requirement to upscale geological models to a structured simulation grid is removed, there is no need to build geological models that are restricted by grid resolution.
Innate Immune Cells in Inflammation and Cancer
Authors: Nowarski Roni , Gagliani Nicola , Huber Samuel , Flavell Richard A. 
Published: August 2013

Abstract
The innate immune system has evolved in multicellular organisms to detect and respond to situations that compromise tissue homeostasis. It comprises a set of tissue-resident and circulating leukocytes primarily designed to sense pathogens and tissue damage through hardwired receptors and eliminate noxious sources by mediating inflammatory processes. While indispensable to immunity, the inflammatory mediators produced in situ by activated innate cells during injury or infection are also associated with increased cancer risk and tumorigenesis. Here, we outline basic principles of innate immune cell functions in inflammation and discuss how these functions converge upon cancer development. Cancer Immunol Res; 1(2); 77–84. ©2013 AACR.
Age-associated pro-inflammatory adaptations of the mouse thoracic aorta
Authors: Hemmeryckx Bianca , Hoylaerts Marc F. , Deloose Eveline , Van Hove Cor E. , Fransen Paul , Bult Hidde , Lijnen H. Roger 
Published: August 2013

SummaryArterial ageing may be associated with a reduction in vasodilation due to increased reactive oxygen species (ROS) production, whereas endothelial cell activation induces procoagulant changes. However, little is known on the effect of ageing on expression of anticoagulant endothelial markers such as endothelial protein C receptor (EPCR). To study age-associated alterations in smooth muscle cell (SMC) and endothelial cell (EC) structure and function, the aorta was isolated from 10-week-and 12– and 24-month-old C57BL/6J mice and analysed for its expression of genes involved in senescence, oxidative stress production, coagulation and matrix remodelling. In addition, vasorelaxation experiments were performed using 10-week-and 24-month-old thoracic aortic ring segments in organ chamber baths. The media thickness of the thoracic aorta progressively increased with age, associated with hypertrophy of vascular SMCs. Basal nitric oxide production and sensitivity to acetylcholine-mediated vasodilation in thoracic aorta rings was reduced with age, whereas no significant differences in ROS production could be demonstrated. Gene expression of tissue factor, EPCR and von Willebrand factor was not affected by ageing of the aorta, whereas that of thrombomodulin was mildly reduced and that of xanthine dehydrogenase, NADPH oxidase 4, tumour necrosis factor-α and vascular cell adhesion molecule-1 significantly enhanced. In conclusion, a reduction in endothelial cell-mediated vasodilation in aged thoracic aortas of C57BL/6J mice was accompanied by a shift towards a pro-inflammatory state of the endothelium.
Identification of poor response to P2Y12 inhibitors in ACS patients with a new ELISA-based vasodilator-associated stimulated phosphoprotein (VASP) phosphorylation assay
Authors: Abtan Jérémie , Silvain Johanne , Kerneis Mathieu , O’Connor Stephen A. , Barthélémy Olivier , Vignalou Jean-Baptiste , Beygui Farzin , Brugier Delphine , Collet Jean-Philippe , Montalescot Gilles 
Published: August 2013

SummaryA new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.
Physician Volume, Specialty, and Outcomes of Care for Patients With Heart Failure
Authors: Joynt Karen E. , Orav E. John , Jha Ashish K. 
Published: August 2013

Background—
There is an urgent need to improve outcomes and reduce costs for patients with heart failure (HF). Physician volume is associated with better outcomes for patients undergoing procedures, but its association with outcomes for medically managed diseases, such as HF, is not well understood.

Methods and Results—

We used Medicare inpatient data in 2009 to examine all HF admissions to acute care hospitals in the United States. We divided physicians into quintiles according to their volume of patients with HF. We used patient-level regression to compare 30-day risk-adjusted mortality, readmissions, and costs across volume groups, controlling for patient, physician, and hospital characteristics. We examined physician volume within strata of hospital volume and physician specialty. Patients cared for by the high-volume physicians had lower mortality than those by the low-volume physicians (8.9% versus 9.7%;
P
<0.001); this relationship was strongest in low-volume hospitals. In contrast, patients cared for by high-volume physicians had higher readmission rates (25.8% versus 21.5%;
P
<0001); this relationship was similar across hospital volume groups. Finally, costs were higher for the high-volume physicians ($8982 versus $8731;
P
=0.002, a difference that was consistent across hospital volume groups). The relationship between physician volume and mortality was strongest for internists (9.2% versus 10.6%;
P
<0.001) and weakest for cardiologists (6.4% versus 6.7%;
P
=0.485).

Conclusions—
Physician volume is associated with lower mortality for HF, particularly in low-volume institutions and among noncardiologist physicians. Our findings suggest that clinician expertise may play an important role in HF care.
The Feminization of Control: Female Militia and Social Order in Iran
Authors: Golkar Saeid 
Published: August 2013

Abstract
The purpose of this article is to analyze the evolution of the Women’s Basij Organization and its role in maintaining social order in Iran. This paper examines how and why the Islamic republic of Iran (IRI) uses female Basij members as agents of social control. During the past three decades, the IRI has recruited and indoctrinated a group of Iranian women through the Women’s Basij Organization, and has used these women to guard Islamic values and manners in Iranian society. In this way, female Basijis have been crucial to the Islamic Republic’s strategy to penetrate Iranian families and institutionalize social and political order in post-revolutionary Iran.
Gravity Wave–Fine Structure Interactions. Part II: Energy Dissipation Evolutions, Statistics, and Implications
Authors: Fritts David C. , Wang Ling 
Published: August 2013

Abstract
Part I of this paper employs four direct numerical simulations (DNSs) to examine the dynamics and energetics of idealized gravity wave–fine structure (GW–FS) interactions. That study and this companion paper were motivated by the ubiquity of multiscale GW–FS superpositions throughout the atmosphere. These DNSs exhibit combinations of wave–wave interactions and local instabilities that depart significantly from those accompanying idealized GWs or mean flows alone, surprising dependence of the flow evolution on the details of the FS, and an interesting additional pathway to instability and turbulence due to GW–FS superpositions. This paper examines the mechanical and thermal energy dissipation rates occurring in two of these DNSs. Findings include 1) dissipation that tends to be much more localized and variable than that due to GW instability in the absence of FS, 2) dissipation statistics indicative of multiple turbulence sources, 3) strong influences of FS shears on instability occurrence and turbulence intensities and statistics, and 4) significant differences between mechanical and thermal dissipation rate fields having potentially important implications for measurements of these flows.
The Influence of the AMOC Variability on the Atmosphere in CCSM3
Authors: Frankignoul Claude , Gastineau Guillaume , Kwon Young-Oh 
Published: August 2013

Abstract
The influence of the Atlantic meridional overturning circulation (AMOC) variability on the atmospheric circulation is investigated in a control simulation of the NCAR Community Climate System Model, version 3 (CCSM3), where the AMOC evolves from an oscillatory regime into a red noise regime. In the latter, an AMOC intensification is followed during winter by a positive North Atlantic Oscillation (NAO). The atmospheric response is robust and controlled by AMOC-driven SST anomalies, which shift the heat release to the atmosphere northward near the Gulf Stream/North Atlantic Current. This alters the low-level atmospheric baroclinicity and shifts the maximum eddy growth northward, affecting the storm track and favoring a positive NAO. The AMOC influence is detected in the relation between seasonal upper-ocean heat content or SST anomalies and winter sea level pressure. In the oscillatory regime, no direct AMOC influence is detected in winter. However, an upper-ocean heat content anomaly resembling the AMOC footprint precedes a negative NAO. This opposite NAO polarity seems due to the southward shift of the Gulf Stream during AMOC intensification, displacing the maximum baroclinicity southward near the jet exit. As the mode has somewhat different patterns when using SST, the wintertime impact of the AMOC lacks robustness in this regime. However, none of the signals compares well with the observed influence of North Atlantic SST anomalies on the NAO because SST is dominated in CCSM3 by the meridional shifts of the Gulf Stream/North Atlantic Current that covary with the AMOC. Hence, although there is some potential climate predictability in CCSM3, it is not realistic.