bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Fringes of Center: Disputed Hagiographic Imagery and the Crisis over theBeati moderniin Rome ca. 1600*
Authors: Noyes Ruth S. 
Published: September 2011

AbstractThis article sets forth, through a small collection of case studies, the extent to which the literal and pictorial figures of theBeati moderniconstituted potentially provocative and disputed hermeneutical territory between particular religious constituencies, in this case the Oratorians and the Jesuits, and an increasingly stringent Curia ca. 1600. A reexamination ofBeati modernihagiographic imagery, and curial censorship of such imagery, potentially problematizes scholarly assumptions that these images served the Counter-Reformation Church's demands to control the meaning of religious images and the cult of the saints. Such reassessment calls for the reevaluation of a newly-constituted, uniquely post-Tridentine genre of hagiographic imagery: theBeati modernidevotional altar image and its reproductive printed devotional derivatives.
Studies on Porcine Circovirus Type 2 Vaccination of 5-Day-Old Piglets
Authors: O'Neill K. C. , Shen H. G. , Lin K. , Hemann M. , Beach N. M. , Meng X. J. , Halbur P. G. , Opriessnig T. 
Published: September 2011

ABSTRACT
Porcine circovirus type 2 (PCV2) vaccines have become widely used since they became available in 2006. It is not uncommon for producers to use PCV2 vaccines in pigs younger than what is approved by manufacturers. The objective of this study was to determine the efficacy of a chimeric and a subunit PCV2 vaccine administered at 5 or 21 days of age. Forty-eight PCV2-naïve piglets were randomly divided into six groups of eight pigs each. Vaccination was done at day 5 or day 21, followed by triple challenge with PCV2, porcine parvovirus (PPV), and porcine reproductive and respiratory syndrome virus (PRRSV) at day 49. Vaccinated pigs seroconverted to PCV2 approximately 14 days postvaccination and had a detectable neutralizing antibody response by 21 days postvaccination regardless of age at vaccination. At day 49, the pigs vaccinated with the chimeric vaccine had significantly higher levels of neutralizing antibodies than the pigs vaccinated with the subunit vaccine. After challenge, vaccinated pigs had significantly decreased levels of PCV2 viremia and a decreased prevalence and severity of microscopic lesions compared to the positive-control group, which had severe lymphoid lesions associated with abundant PCV2 antigen, compatible with PCV-associated disease. The results of this study indicate that, under the conditions of this study, vaccination of PCV2-naïve pigs at day 5 or day 21 resulted in development of a detectable humoral immune response and provided reduction or complete protection against PCV2 viremia and PCV2-associated lesions after triple challenge with PCV2, PPV, and PRRSV.
Comparison of a Newly Developed Automated and Quantitative Hepatitis C Virus (HCV) Core Antigen Test with the HCV RNA Assay for Clinical Usefulness in Confirming Anti-HCV Results
Authors: Kesli Recep , Polat Hakkı , Terzi Yuksel , Kurtoglu Muhammet Guzel , Uyar Yavuz 
Published: September 2011

ABSTRACT

Hepatitis C virus (HCV) is a global health care problem. Diagnosis of HCV infection is mainly based on the detection of anti-HCV antibodies as a screening test with serum samples. Recombinant immunoblot assays are used as supplemental tests and for the final detection and quantification of HCV RNA in confirmatory tests. In this study, we aimed to compare the HCV core antigen test with the HCV RNA assay for confirming anti-HCV results to determine whether the HCV core antigen test may be used as an alternative confirmatory test to the HCV RNA test and to assess the diagnostic values of the total HCV core antigen test by determining the diagnostic specificity and sensitivity rates compared with the HCV RNA test. Sera from a total of 212 treatment-naive patients were analyzed for anti-HCV and HCV core antigen both with the Abbott Architect test and with the molecular HCV RNA assay consisting of a reverse transcription-PCR method as a confirmatory test. The diagnostic sensitivity, specificity, and positive and negative predictive values of the HCV core antigen assay compared to the HCV RNA test were 96.3%, 100%, 100%, and 89.7%, respectively. The levels of HCV core antigen showed a good correlation with those from the HCV RNA quantification (
r
= 0.907). In conclusion, the Architect HCV antigen assay is highly specific, sensitive, reliable, easy to perform, reproducible, cost-effective, and applicable as a screening, supplemental, and preconfirmatory test for anti-HCV assays used in laboratory procedures for the diagnosis of hepatitis C virus infection.
Cell-to-Cell Contact with Hepatitis C Virus-Infected Cells Reduces Functional Capacity of Natural Killer Cells
Authors: Yoon Joo Chun , Lim Jong-Baeck , Park Jeon Han , Lee Jae Myun 
Published: September 2011

ABSTRACT

The distinct feature of hepatitis C virus (HCV) infection is a high incidence of chronicity. The reason for chronic HCV infection has been actively investigated, and impairment of innate and adaptive immune responses against HCV is proposed as a plausible cause. Whereas functional impairment of HCV-specific T cells is well characterized, the role and functional status of natural killer (NK) cells in each phase of HCV infection are still elusive. We therefore investigated whether direct interaction between NK cells and HCV-infected cells modulates NK cell function. HCV-permissive human hepatoma cell lines were infected with cell culture-generated HCV virions and cocultured with primary human NK cells. Cell-to-cell contact between NK cells and HCV-infected cells reduced NK cells' capacity to degranulate and lyse target cells, especially in the CD56
dim
NK cell subset, which is characterized by low-density surface expression of CD56. The decrease in degranulation capacity was correlated with downregulated expression of NK cell-activating receptors, such as NKG2D and NKp30, on NK cells. The ability of NK cells to produce and secrete gamma interferon (IFN-γ) also diminished after exposure to HCV-infected cells. The decline of IFN-γ production was consistent with the reduction of NK cell degranulation. In conclusion, cell-to-cell contact with HCV-infected cells negatively modulated functional capacity of NK cells, and the inhibition of NK cell function was associated with downregulation of NK-activating receptors on NK cell surfaces. These observations suggest that direct cell-to-cell interaction between NK cells and HCV-infected hepatocytes may impair NK cell function
in vivo
and thereby contribute to the establishment of chronic infection.
HIV-1 Infection Abrogates CD8+T Cell Mitogen-Activated Protein Kinase Signaling Responses
Authors: Crawford Timothy Q. , Ndhlovu Lishomwa C. , Tan Alice , Carvidi Alex , Hecht Frederick M. , Sinclair Elizabeth , Barbour Jason D. 
Published: September 2011

ABSTRACTMitogen-activated protein kinase (MAPK) signaling pathways are dynamic and sensitive regulators of T cell function and differentiation. Altered MAPK signaling has been associated with the inflammatory and autoimmune diseases lupus and arthritis and with some pathogenic viral infections. HIV-1 infection is characterized by chronic immune inflammation, aberrantly heightened CD8+T cell activation levels, and altered T cell function. The relationship between MAPK pathway function, HIV-1-induced activation (CD38 and HLA-DR), and exhaustion (Tim-3) markers in circulating CD8+T cells remains unknown. Phosphorylation of the MAPK effector proteins ERK and p38 was examined by “phosflow” flow cytometry in 79 recently HIV-1-infected, antiretroviral-treatment-naïve adults and 21 risk-matched HIV-1-negative controls. We identified a subset of CD8+T cells refractory to phorbol 12-myristate 13-acetate plus ionomycin-induced ERK1/2 phosphorylation (referred to as p-ERK1/2-refractory cells) that was greatly expanded in HIV-1-infected adults. The CD8+p-ERK1/2-refractory cells were highly activated (CD38+HLA-DR+) but not exhausted (Tim-3 negative), tended to have low CD8 expression, and were enriched in intermediate and late transitional memory states of differentiation (CD45RA−CD28−CD27+/−). Targeting MAPK pathways to restore ERK1/2 signaling may normalize immune inflammation levels and restore CD8+T cell function during HIV-1 infection.
Immunopathogenic and Antibacterial Effects of H3N2 Influenza A Virus PB1-F2 Map to Amino Acid Residues 62, 75, 79, and 82
Authors: Alymova Irina V. , Green Amanda M. , van de Velde Nicholas , McAuley Julie L. , Boyd Kelli L. , Ghoneim Hazem E. , McCullers Jonathan A. 
Published: September 2011

ABSTRACT

The influenza A virus protein PB1-F2 has been linked to the pathogenesis of both primary viral and secondary bacterial infections. H3N2 viruses have historically expressed full-length PB1-F2 proteins with either proinflammatory (e.g., from influenza A/Hong Kong/1/1968 virus) or noninflammatory (e.g., from influenza A/Wuhan/359/1995 virus) properties. Using synthetic peptides derived from the active C-terminal portion of the PB1-F2 protein from those two viruses, we mapped the proinflammatory domain to amino acid residues L62, R75, R79, and L82 and then determined the role of that domain in H3N2 influenza virus pathogenicity. PB1-F2-derived peptides containing that proinflammatory motif caused significant morbidity, mortality, and pulmonary inflammation in mice, manifesting as increased acute lung injury and the presence of proinflammatory cytokines and inflammatory cells in the lungs compared to peptides lacking this motif, and better supported bacterial infection with
Streptococcus pneumoniae
. Infections of mice with an otherwise isogenic virus engineered to contain this proinflammatory sequence in PB1-F2 demonstrated increased morbidity resulting from primary viral infections and enhanced development of secondary bacterial pneumonia. The presence of the PB1-F2 noninflammatory (P62, H75, Q79, and S82) sequence in the wild-type virus mediated an antibacterial effect. These data suggest that loss of the inflammatory PB1-F2 phenotype that supports bacterial superinfection during adaptation of H3N2 viruses to humans, coupled with acquisition of antibacterial activity, contributes to the relatively diminished frequency of severe infections seen with seasonal H3N2 influenza viruses in recent decades compared to their first 2 decades of circulation.
c-Cbl-Mediated Selective Virus-Receptor Translocations into Lipid Rafts Regulate Productive Kaposi's Sarcoma-Associated Herpesvirus Infection in Endothelial Cells
Authors: Chakraborty Sayan , ValiyaVeettil Mohanan , Sadagopan Sathish , Paudel Nitika , Chandran Bala 
Published: September 2011

ABSTRACT

During target cell entry and infection, many enveloped and nonenveloped viruses utilize cell surface receptors that translocate into lipid rafts (LRs). However, the mechanism behind this translocation is not known. Kaposi's sarcoma-associated herpesvirus (KSHV) interacts with the human microvascular dermal endothelial (HMVEC-d) cell surface heparan sulfate (HS), integrins α3β1, αVβ3, and αVβ5, and the amino acid transporter x-CT protein and enters via c-Cbl-bleb-mediated macropinocytosis (Veettil et al., J. Virol.
82:
12126-12144, 2008; Veettil et al., PLoS Pathog.
6:
e1001238, 2010). Here we have demonstrated that very early during infection (1 min postinfection), c-Cbl induced the selective translocation of KSHV into the LR along with the α3β1, αVβ3, and x-CT receptors but not αVβ5. Activated c-Cbl localized with LRs at the junctional base of macropinocytic blebs. LR-translocated α3β1 and αVβ3 were monoubiquitinated, leading to productive macropinocytic entry, whereas non-LR-associated αVβ5 was polyubiquitinated, leading to clathrin entry that was targeted to lysosomes. c-Cbl knockdown blocked the macropinocytosis and receptor translocation and diverted KSHV to a clathrin-lysosomal noninfectious pathway. Similar results were also seen by LR disruption with MβCD. These studies provide the first evidence that c-Cbl regulates selective KSHV-α3β1, -αVβ3, and -x-CT receptor translocations into the LRs and differential ubiquitination of receptors which are critical determinants of the macropinocytic entry route and productive infection of KSHV. Our studies suggest that interventions targeting c-Cbl and LRs are potential avenues to block KSHV infection of endothelial cells.
Tumor-Surrogate Blood Vessel Subtypes Exhibit Differential Susceptibility to Anti-VEGF Therapy
Authors: Sitohy Basel , Nagy Janice A. , Jaminet Shou-Ching Shih , Dvorak Harold F. 
Published: September 2011

Abstract
Antivascular therapy directed against VEGF or its receptors (VEGFR) has been successful when administered at early stages of tumor vessel growth but is less effective when administered later. Tumor blood vessels are heterogeneous, so vessel subpopulations may differ in their requirements for tumor cell–secreted VEGF and in their susceptibility to anti-VEGF/VEGFR therapy. Human cancers contain several distinct blood vessel types, including mother vessels (MV), glomeruloid microvascular proliferations (GMP), vascular malformations (VM), feeding arteries (FA), and draining veins (DV), all of which can be generated in mice in the absence of tumor cells using expression vectors for VEGF-A164. In this study, we investigated the sensitivity of each of these vessel types to anti-VEGF therapy with Aflibercept (VEGF Trap), a potent inhibitor of VEGF-A164. Administering VEGF Trap treatment before or shortly after injection of a recombinant VEGF-A164–expressing adenovirus could prevent or regress tumor-free neovasculature, but it was progressively less effective if initiated at later times. Early-forming MVs and GMPs in which the lining endothelial cells expressed high levels of VEGFR-2 were highly susceptible to blockade by VEGF Trap. In contrast, late-forming VMs, FAs, and DVs that expressed low levels of VEGFR-2 were largely resistant. Together, our findings define the susceptibility of different blood vessel subtypes to anti-VEGF therapy, offering a possible explanation for the limited effectiveness of anti-VEGF-A/VEGFR treatment of human cancers, which are typically present for months to years before discovery and are largely populated by late-forming blood vessels. Cancer Res; 71(22); 7021–8. ©2011 AACR.
Evaluating the role for the optical density in the diagnosis of heparin-induced thrombocytopenia following cardiac surgery
Authors: Chan Chee , Corso Paul , Sun Xiumei , Hill Peter , Shorr Andrew 
Published: September 2011

SummaryThe poor accuracy of the enzyme immune assay (EIA) contributes to the diagnostic challenge of heparin-induced thrombocytopenia (HIT) following cardiac surgery. We sought to determine if adjusting the threshold optical density (OD) defining a positive EIA improves the test's accuracy in subjects with an OD>0.40. We retrospectively analysed the results from both EIA and confirmatory serotonin release assays (SRAs) in cardiac surgery patients with EIA OD of >0.4. Employing the SRA as the standard, we compared the area under the receiver-operating characteristic (AUROC) curves of various OD measurements for identifying HIT. We examined baseline clinical variables associated with a positive SRA in the setting of a positive HIT EIA (OD >0.4). We then used logistic regression to identify baseline clinical variables independently associated with a positive SRA given a positive EIA. The cohort included 99 subjects with positive EIAs and 35% had positive SRAs. An OD>0.40 had moderate utility as a screening test for a positive SRA (AUROC: 0.68; 95% CI: 0.55–0.80). Increasing the OD threshold did not improve the HIT EIA's screening utility. Clinical variables independently associated with a positive SRA if the EIA were positive included female gender, absence of diabetes, and use of cardiopulmonary bypass. A relatively modest elevation in the OD measurement, when it is already known to be greater than 0.4, does not reliably exclude the potential for a positive SRA in this setting.
Current views on the functions of interleukin-17A-producing cells in atherosclerosis
Authors: Butcher Matthew , Galkina Elena 
Published: September 2011

SummaryMultiple components of the immune response are involved in the initiation, progression and persistence of atherosclerosis. Interleukin (IL)-17A is produced by a broad variety of leukocytes and plays an important role in host defense. IL-17A is also involved in the pathology of several autoimmune diseases mainly via the regulation of chemokine expression and leukocyte migration to the site of inflammation. There is an increasing body of evidence indicating an association between elevated levels of IL-17A and cardiovascular diseases. Interestingly, this IL- 17A-dependent response occurs in parallel with the Th1-dominant immune response during atherogenesis. To date, the precise role of IL-17A+ cells in atherosclerosis is controversial. Several studies have suggested a pro-atherogenic role of IL-17A via the regulation of aortic macrophage numbers, Th1-related cytokines and aortic chemokine expression. However, two studies recently described anti-inflammatory effects of IL-17A on mouse plaque burden via possible regulation of aortic VCAM-1 expression and T cell content. Furthermore, an initial study using IL-17A-deficient mice demonstrated that IL-17A affects the immune composition and inflammatory phenotype of the aortic wall; however, no effects were observed on atherosclerosis. Further studies are necessary to fully address the role of IL-17A and other IL-17 family members in atherosclerosis.
Functional PU.1 in macrophages has a pivotal role in NF-κB activation and neutrophilic lung inflammation during endotoxemia
Authors: Karpurapu Manjula , Wang Xuerong , Deng Jing , Park Hyesuk , Xiao Lei , Sadikot Ruxana T. , Frey Randall S. , Maus Ulrich A. , Park Gye Young , Scott Edward W. , Christman John W. 
Published: September 2011

AbstractAlthough the role of ETS family transcriptional factor PU.1 is well established in macrophage maturation, its role in mature macrophages with reference to sepsis- related animal model has not been elucidated. Here, we report the in vivo function of PU.1 in mediating mature macrophage inflammatory phenotype by using bone marrow chimera mice with conditional PU.1 knockout. We observed that the expression of monocyte/macrophage-specific markers CD 11b, F4/80 in fetal liver cells, and bone marrow–derived macrophages were dependent on functional PU.1. Systemic inflammation as measured in terms of NF-κB reporter activity in lung, liver, and spleen tissues was significantly decreased in PU.1-deficient chimera mice compared with wild-type chimeras on lipopolysaccharide (LPS) challenge. Unlike wild-type chimera mice, LPS challenge in PU.1-deficient chimera mice resulted in decreased lung neu-trophilic inflammation and myeloperoxidase activity. Similarly, we found attenuated inflammatory gene expression (cyclooxygenase-2, inducible nitric-oxide synthase, and TLR4) and inflammatory cytokine secretion (IL-6, MCP-1, IL-1β, TNF-α, and neutrophilic chemokine keratinocyte-derived chemokine) in PU.1-deficient mice. Most importantly, this attenuated lung and systemic inflammatory phenotype was associated with survival benefit in LPS-challenged heterozygotic PU.1-deficient mice, establishing a novel protective mechanistic role for the lineage-specific transcription factor PU.1.
PIM2 inhibition as a rational therapeutic approach in B-cell lymphoma
Authors: Gómez-Abad Cristina , Pisonero Helena , Blanco-Aparicio Carmen , Roncador Giovanna , González-Menchén Alberto , Martinez-Climent Jose A. , Mata Eva , Rodríguez María Elena , Muñoz-González Guillermo , Sánchez-Beato Margarita , Leal Juan F. , Bischoff James R. , Piris Miguel A. 
Published: September 2011

AbstractPIM serine/threonine kinases are overexpressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa–associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification.
High BRE expression predicts favorable outcome in adult acute myeloid leukemia, in particular among MLL-AF9–positive patients
Authors: Noordermeer Sylvie M. , Sanders Mathijs A. , Gilissen Christian , Tönnissen Evelyn , van der Heijden Adrian , Döhner Konstanze , Bullinger Lars , Jansen Joop H. , Valk Peter J. M. , van der Reijden Bert A. 
Published: September 2011

Abstract
Aberrations in protein ubiquitination have recently been identified in the pathogenesis of acute myeloid leukemia (AML). We studied whether expression changes of more than 1600 ubiquitination related genes correlated with clinical outcome in 525 adult AML patients. High expression of one of these genes, BRE, was observed in 3% of the cases and predicted favorable prognosis independently of known prognostic factors (5-year overall survival: 57%). Remarkably, unsupervised expression profiling showed that 86% of high BRE-expressing patients were confined to a previously unrecognized cluster. High BRE expression was mutually exclusive with FLT3 ITD, CEBPA, IDH1, and IDH2 mutations, EVI1 overexpression, and favorable karyotypes. In contrast, high BRE expression co-occurred strongly with FAB M5 morphology and MLL-AF9 fusions. Within the group of MLL-AF9–positive patients, high BRE expression predicted superior survival, while normal BRE expression predicted extremely poor survival (5-year overall survival of 80% vs 0%, respectively, P = .0002). Both the co-occurrence of high BRE expression with MLL-AF9 and its prognostic impact were confirmed in an independent cohort of 436 AML patients. Thus, high BRE expression defines a novel subtype of adult AML characterized by a favorable prognosis. This work contributes to improved risk stratification in AML, especially among MLL-AF9–positive patients.