bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Evaluation of Two Hemagglutinating Encephalomyelitis Coronavirus Vaccine Candidates in Mice
Authors: Chen Keyan , Zhao Kui , He Wenqi , Gao Wei , Zhao Chuanbo , Wang Li , Pan Wei , Song Deguang , Wang Chengli , Gao Feng 
Published: April 2012

ABSTRACTPorcine hemagglutinating encephalomyelitis (PHE) is caused by the coronavirus hemagglutinating encephalomyelitis virus (PHE-CoV), and the recent, rapid spread of PHE-CoV in piglets from many countries emphasizes the urgent need for a PHE-CoV vaccine. Here we use a murine model for evaluation of the induction of humoral and cellular immune responses by inactivated and PHE-CoV DNA vaccines in order to define the immune correlates for protection against PHE-CoV. The inactivated vaccine was composed of purified PHE-CoV and aluminum hydroxide gel (alum), which was chosen as an adjuvant because of its long history of safety for human use. The PHE-CoV DNA vaccine was constructed by subcloning the S1 gene of PHE-CoV into the pVAX1 vector to create the recombinant plasmid pV-S1. Our results showed that the inactivated PHE-CoV vaccine (IPV) elicited a high level of humoral immunity, resulting in good protection efficacy against PHE-CoV challenge. The IPV induced the IgG1 subclass of serum antibodies and expression of the cytokine interleukin-4 (IL-4), suggesting that the IPV generated a predominantly Th2-type immune response. The DNA vaccine was found to mediate primarily a cellular immune response with high levels of IgG2a and the cytokines IL-2 and gamma interferon (IFN-γ). However, mice that were vaccinated twice with the DNA vaccine and boosted with the IPV could mount a sufficient neutralizing antibody response against live PHE-CoV, with little variation in IgG1 and IgG2a levels, and showed high levels of IL-2 and IL-4. This response may activate both B and T cells to mount a specific humoral and cellular immune response that could, in turn, elicit a phagocyte-mediated defense against PHE-CoV infections to achieve viral clearance.
Outbreak of Transient Conversions of the QuantiFERON-TB Gold In-Tube Test in Laboratory Health Care Worker Screenings
Authors: Zanetti Caterina , Peracchi Marta , Zorzi Diego , Fiorio Silvia , Fallico Loredana , Palù Giorgio 
Published: April 2012

ABSTRACT

Gamma interferon release assays were recently introduced in health care worker (HCWs) screenings for tuberculosis surveillance. In longitudinal surveys, conversions and reversions are seen, and yet whether these changes are unspecific or are an expression of new infections and microbial clearance remains unclear. In order to further elucidate these changes, we analyzed an outbreak of 15 transient conversions in 53 HCWs who operate in the same laboratory and handle specimens potentially containing
Mycobacterium tuberculosis
who underwent screening by the QuantiFERON-TB Gold In-Tube (QFT-GIT) test between 11 May and 30 June 2010: 15/46 (33%) negative HCWs showed a conversion and then reverted after 7 to 107 days. To validate these results, an evaluation of methodological procedures and test reliability, as well as an analysis of results obtained during the same period and processed by the same laboratory, was carried out. For the latter purpose, QFT-GIT results determined for 78 ward HCWs who underwent screening during the same period and were employed in departments with at least 3 infectious tuberculosis patients per year or had cared for an infectious patient without airborne precautions were analyzed with the following results: 6/63 (9%) HCWs with negative results in 3 different departments showed transient conversion (
P
= 0.002; odds ratio, 4.60; 95% confidence interval, 1.62 to 13.04). A retrospective survey of in-house biosafety practices led to determination of a single exposure factor within the laboratory. These data emphasize the validity of the hypothesis that a transient conversion demonstrates the presence of a real tubercular infection and could be an important indicator for occupational biosafety concerns. They also confirm that subjects with recent conversion should be retested before chest radiography and chemotherapy is offered.
Epstein-Barr Virus Latent Membrane Protein 2A Promotes Invasion of Nasopharyngeal Carcinoma Cells through ERK/Fra-1-Mediated Induction of Matrix Metalloproteinase 9
Authors: Lan Yu-Yan , Hsiao Jenn-Ren , Chang Kung-Chao , Chang Jeffrey Shu-Ming , Chen Chaio-Wei , Lai Hsiao-Ching , Wu Shih-Yi , Yeh Tzu-Hao , Chang Fang-Hsin , Lin Wei-Hung , Su Ih-Jen , Chang Yao 
Published: April 2012

ABSTRACT
Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) is highly metastatic, and this malignant feature may be promoted by an EBV oncoprotein, latent membrane protein 2A (LMP2A). Acting as a signal regulator, LMP2A can enhance invasiveness and motility of epithelial cells. Downstream from the LMP2A-triggered signaling events, it is largely unknown what key effector proteins are induced and essentially promote cell invasion. In the present study, we found that in NPC cells, LMP2A upregulated matrix metalloproteinase 9 (MMP9), a metastasis-associated protease. LMP2A increased MMP9 expression at both the mRNA and protein levels. It also activated the MMP9 promoter, in which two AP-1 elements were required for the promoter activation. Among AP-1 transcription factors, Fra-1 was induced by LMP2A and is essential for LMP2A-triggered MMP9 expression. Induction of Fra-1 was dependent on the LMP2A-activated ERK1/2 pathway, and induction of the ERK1/2–Fra-1–MMP9 axis required PY motifs in the amino-terminal domain of LMP2A. Notably, LMP2A-promoted invasion of NPC cells was blocked when MMP9 expression, Fra-1 induction, or ERK1/2 activation was inhibited. In addition, we found an association of LMP2A with MMP9 expression in NPC tumor biopsy specimens, where Fra-1 was a major mediation factor. This study reveals an underlying mechanism of LMP2A-induced cell invasion, from signal transduction to upregulation of a critical protease. Considering that MMP9 can also be upregulated by another EBV oncoprotein, LMP1, this protease may be a pivotal effector at which the EBV-induced, invasion-promoting mechanisms converge, serving as an attractive therapeutic target for NPC treatment.
Genomic Sequences of Australian Bluetongue Virus Prototype Serotypes Reveal Global Relationships and Possible Routes of Entry into Australia
Authors: Boyle David B. , Bulach Dieter M. , Amos-Ritchie Rachel , Adams Mathew M. , Walker Peter J. , Weir Richard 
Published: April 2012

ABSTRACT

Bluetongue virus (BTV) is transmitted by biting midges (
Culicoides
spp.). It causes disease mainly in sheep and occasionally in cattle and other species. BTV has spread into northern Europe, causing disease in sheep and cattle. The introduction of new serotypes, changes in vector species, and climate change have contributed to these changes. Ten BTV serotypes have been isolated in Australia without apparent associated disease. Simplified methods for preferential isolation of double-stranded RNA (dsRNA) and template preparation enabled high-throughput sequencing of the 10 genome segments of all Australian BTV prototype serotypes. Phylogenetic analysis reinforced the Western and Eastern topotypes previously characterized but revealed unique features of several Australian BTVs. Many of the Australian BTV genome segments (Seg-) were closely related, clustering together within the Eastern topotypes. A novel Australian topotype for Seg-5 (NS1) was identified, with taxa spread across several serotypes and over time. Seg-1, -2, -3, -4, -6, -7, -9, and -10 of BTV_2_AUS_2008 were most closely related to the cognate segments of viruses from Taiwan and Asia and not other Australian viruses, supporting the conclusion that BTV_2 entered Australia recently. The Australian BTV_15_AUS_1982 prototype was revealed to be unusual among the Australian BTV isolates, with Seg-3 and -8 distantly related to other BTV sequences from all serotypes.
Structural Analysis of Coxsackievirus A7 Reveals Conformational Changes Associated with Uncoating
Authors: Seitsonen Jani J. T. , Shakeel Shabih , Susi Petri , Pandurangan Arun P. , Sinkovits Robert S. , Hyvönen Heini , Laurinmäki Pasi , Ylä-Pelto Jani , Topf Maya , Hyypiä Timo , Butcher Sarah J. 
Published: April 2012

ABSTRACTCoxsackievirus A7 (CAV7) is a rarely detected and poorly characterized serotype of theEnterovirusspeciesHuman enterovirus A(HEV-A) within thePicornaviridaefamily. The CAV7-USSR strain has caused polio-like epidemics and was originally thought to represent the fourth poliovirus type, but later evidence linked this strain to the CAV7-Parker prototype. Another isolate, CAV7-275/58, was also serologically similar to Parker but was noninfectious in a mouse model. Sequencing of the genomic region encoding the capsid proteins of the USSR and 275/58 strains and subsequent comparison with the corresponding amino acid sequences of the Parker strain revealed that the Parker and USSR strains are nearly identical, while the 275/58 strain is more distant. Using electron cryomicroscopy and three-dimensional image reconstruction, the structures of the CAV7-USSR virion and empty capsid were resolved to 8.2-Å and 6.1-Å resolutions, respectively. This is one of the first detailed structural analyses of theHEV-Aspecies. Using homology modeling, reconstruction segmentation, and flexible fitting, we constructed a pseudoatomic T = 1 (pseudo T = 3) model incorporating the three major capsid proteins (VP1 to VP3), addressed the conformational changes of the capsid and its constituent viral proteins occurring during RNA release, and mapped the capsid proteins' variable regions to the structure. During uncoating, VP4 and RNA are released analogously to poliovirus 1, the interfaces of VP2 and VP3 are rearranged, and VP1 rotates. Variable regions in the capsid proteins were predicted to map mainly to the surface of VP1 and are thus likely to affect the tropism and pathogenicity of CAV7.
Pellino-1 Selectively Regulates Epithelial Cell Responses to Rhinovirus
Authors: Bennett Julie A. , Prince Lynne R. , Parker Lisa C. , Stokes Clare A. , de Bruin Harold G. , van den Berge Maarten , Heijink Irene H. , Whyte Moira K. , Sabroe Ian 
Published: April 2012

ABSTRACT
Pellino-1 has recently been identified as a regulator of interleukin-1 (IL-1) signaling, but its roles in regulation of responses of human cells to human pathogens are unknown. We investigated the potential roles of Pellino-1 in the airways. We show for the first time that Pellino-1 regulates responses to a human pathogen, rhinovirus minor group serotype 1B (RV-1B). Knockdown of Pellino-1 by small interfering RNA (siRNA) was associated with impaired production of innate immune cytokines such as CXCL8 from human primary bronchial epithelial cells in response to RV-1B, without impairment in production of antiviral interferons (IFN), and without loss of control of viral replication. Pellino-1 actions were likely to be independent of interleukin-1 receptor-associated kinase-1 (IRAK-1) regulation, since Pellino-1 knockdown in primary epithelial cells did not alter responses to IL-1 but did inhibit responses to poly(I·C), a Toll-like receptor 3 (TLR3) activator that does not signal via IRAK-1 to engender a response. These data indicate that Pellino-1 represents a novel target that regulates responses of human airways to human viral pathogens, independently of IRAK signaling. Neutralization of Pellino-1 may therefore provide opportunities to inhibit potentially harmful neutrophilic inflammation of the airways induced by respiratory viruses, without loss of control of the underlying viral infection.
The Ubiquitin-Specific Protease USP7 Modulates the Replication of Kaposi's Sarcoma-Associated Herpesvirus Latent Episomal DNA
Authors: Jäger Wiebke , Santag Susann , Weidner-Glunde Magdalena , Gellermann Eva , Kati Semra , Pietrek Marcel , Viejo-Borbolla Abel , Schulz Thomas F. 
Published: April 2012

ABSTRACT

Kaposi's sarcoma herpesvirus (KSHV) belongs to the gamma-2
Herpesviridae
and is associated with three neoplastic disorders: Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD). The viral latency-associated nuclear antigen 1 (LANA) is expressed in all latently KSHV-infected cells and is involved in viral latent replication and maintenance of the viral genome. We show that LANA interacts with the ubiquitin-specific protease USP7 through its N-terminal TRAF (tumor necrosis factor [TNF] receptor-associated factor) domain. This interaction involves a short sequence (amino acids [aa] 971 to 986) within the C-terminal domain of LANA with strong similarities to the USP7 binding site of the Epstein-Barr virus (EBV) EBNA-1 protein. A LANA mutant with a deletion of the identified USP7 binding site showed an enhanced ability to replicate a plasmid containing the KSHV latent origin of replication but was comparable to the wild-type LANA (LANA WT) with regard to the regulation of viral and cellular promoters. Furthermore, the LANA homologues of two other gamma-2 herpesviruses, MHV68 and RRV, also recruit USP7. Our findings suggest that recruitment of USP7 to LANA could play a role in the regulation of viral latent replication. The recruitment of USP7, and its role in herpesvirus latent replication, previously described for the latent EBNA-1 protein of the gamma-1 herpesvirus (lymphocryptovirus) EBV (M. N. Holowaty et al., J. Biol. Chem. 278:29987–29994, 2003), may thereby be a conserved feature among gammaherpesvirus latent origin binding proteins.
The trajectory to diagnosis with pulmonary arterial hypertension: a qualitative study
Authors: Armstrong Ian , Rochnia Nikki , Harries Carl , Bundock Sarah , Yorke Janelle 
Published: April 2012

ObjectivesTo investigate the patient's experience of the trajectory to receiving a diagnosis of pulmonary arterial hypertension (PAH) and inform the provision of care for this patient group.DesignQualitative study using in-depth one-to-one interviews and pictorial representations. Data were analysed using thematic analysis.SettingParticipants were interviewed in their own homes across England.Participants30 patients with a diagnosis of pulmonary hypertension (18 participants were women, mean age 56 and range 26-80 years and time since diagnosis ranged from a few months to more than 12 years) participated.ResultsAll participants, regardless of the time since diagnosis, vividly described the process from manifestation of symptoms to receiving a confirmed diagnosis. The authors present data using three major themes: (i) making sense of symptoms, (ii) process of elimination and (iii) being diagnosed with PAH. Making sense of symptoms represented an early period of perseverance—people tried to carry-on as usual despite ‘unexplained breathlessness’. As time progressed, this period was punctuated by critical events that triggered seeking medical advice. Once medical contact had been made, patients described a period of ‘elimination’ and convoluted contact with the medical profession. Dyspnoea misdiagnosis was a key factor that delayed the PAH diagnosis. Diagnosis disclosure by some medical professionals was also viewed as lacking empathy. More positive experiences were relayed when the medical team disclosing the diagnosis acknowledged previous limitations.ConclusionsA lack of awareness of this illness from both the sufferer themselves and the medical profession emerged as a central theme and led to prolonged periods of being misdiagnosed. The application of a diagnostic pathway for unexplained dyspnoea that alerts practitioners to rare conditions could expedite the process of correct diagnosis.
PRACTICE SELECTION FRAMEWORK
Authors: IVARSSON MARTIN , GORSCHEK TONY 
Published: April 2012

Knowledge management (KM) in software engineering and software process improvement (SPI) are challenging. Most existing KM and SPI frameworks are too expensive to deploy or do not take an organization's specific needs or knowledge into consideration. There is thus a need for scalable improvement approaches that leverage knowledge already residing in the organizations.This paper presents the Practice Selection Framework (PSF), an Experience Factory approach, enabling lightweight experience capture and use by utilizing postmortem reviews. Experiences gathered concern performance and applicability of practices used in the organization, gained from concluded projects. Project managers use these as decision support for selecting practices to use in future projects, enabling explicit knowledge transfer across projects and the development organization as a whole. Process managers use the experiences to determine if there is potential for improvement of practices used in the organization. This framework was developed and subsequently validated in industry to get feedback on usability and usefulness from practitioners. The validation consisted of tailoring and testing the framework using real data from the organization and comparing it to current practices used in the organization to ensure that the approach meets industry needs. The results from the validation are encouraging and the participants' assessment of PSF and particularly the tailoring developed was positive.
MODELING, DEPLOYING, AND CONTROLLING VOLATILE FUNCTIONALITIES IN WEB APPLICATIONS
Authors: URBIETA MATIAS , ROSSI GUSTAVO , DISTANTE DAMIANO , GINZBURG JERONIMO 
Published: April 2012

One of the main characteristics of most Web applications is their high dynamism. Once implemented and deployed for the first time, new functionalities are added to meet new or changed requirements. Some of these functionalities may appear on the Web in response to an unexpected event, or phenomena (such as a natural calamity) after which they are removed. Some others are activated periodically, to coincide with a particular date, or period of the year (such as, return to school, Christmas holidays, etc.). Implementing such volatile functionalities usually impacts on a number of aspects of a Web application, including content, navigation, presentation, business processes, and user operations. Their cyclic activation/deactivation, which requires repetitive changes in the application code, may be the cause of waste of effort and application quality deterioration, up to incorrect functioning. In this paper, we present an approach to decouple the design and implementation of volatile functionalities from that of stable ones, i.e. the core functionalities of the application. The approach is instantiated in the context of the Object-Oriented Hypermedia Design Method (OOHDM), but its principles and related techniques are generally applicable to any other Web engineering method. We show how our approach enables the deployment and removal of these functionalities in a cost-effective and safe way and at runtime, thus providing business agility. A framework to classify volatile functionalities and a number of examples are also reported.
Decreased Selenium-Binding Protein 1 Enhances Glutathione Peroxidase 1 Activity and Downregulates HIF-1α to Promote Hepatocellular Carcinoma Invasiveness
Authors: Huang Cheng , Ding Guangyu , Gu Chengyu , Zhou Jian , Kuang Ming , Ji Yuan , He Yifeng , Kondo Tadashi , Fan Jia 
Published: April 2012

Abstract
Purpose: We aimed to characterize the role of selenium-binding protein 1 (SBP1) in hepatocellular carcinoma (HCC) invasiveness and underlying clinical significance.
Experimental Design: SBP1 expression was measured in stepwise metastatic HCC cell lines by Western blotting. The role of SBP1 in HCC was investigated using siRNA. Immunofluorescence analyses were used to detect the interaction between SBP1 and glutathione peroxidase 1 (GPX1). Nineteen fresh tumor tissues and 323 paraffin-embedded samples were used to validate in vitro findings and to detect the prognostic significance of SBP1, respectively.
Results: Inhibition of SBP1 effectively increased cell motility, promoted cell proliferation, and inhibited apoptosis only under oxidative stress; it also greatly enhanced GPX1 activity without altering GPX1 expression and downregulated hypoxia-inducible factor-1α (HIF-1α) expression. SBP1 and GPX1 formed nuclear bodies and colocalized under oxidative stress. In freshly isolated clinical HCC tissues, decreased SBP1 was linked with increased GPX1 activity and correlated with vascular invasion. Tumor tissue microarrays indicated that SBP1 was an independent risk factor for overall survival and disease recurrence; patients with lower SBP1 expression experienced shorter overall survival periods and higher rates of disease recurrence (P &lt; 0.001). Further analyses indicated that the predictive power of SBP1 was more significant for patients beyond the Milan criteria than patients within the Milan criteria.
Conclusions: Decreased expression of SBP1 could promote tumor invasiveness by increasing GPX1 activity and diminishing HIF-1α expression in HCC; SBP1 could be a novel biomarker for predicting prognosis and guiding personalized therapeutic strategies, especially in patients with advanced HCC. Clin Cancer Res; 18(11); 3042–53. ©2012 AACR.
Heparanase-Induced GEF-H1 Signaling Regulates the Cytoskeletal Dynamics of Brain Metastatic Breast Cancer Cells
Authors: Ridgway Lon D. , Wetzel Michael D. , Ngo Jason A. , Erdreich-Epstein Anat , Marchetti Dario 
Published: April 2012

Abstract
Heparanase is the only mammalian endoglycosidase which has been widely implicated in cancer because of its capability to degrade heparan sulfate chains of heparan sulfate proteoglycans (HSPG). Specifically, the cell surface HSPG syndecan-1 and -4 (SDC1 and SDC4) are modulators of growth factor action, and SDC4 is implicated in cell adhesion as a key member of focal adhesion complexes. We hypothesized that extracellular heparanase modulates brain metastatic breast cancer (BMBC) cell invasiveness by affecting cytoskeletal dynamics, SDC4 carboxy-terminal–associated proteins, and downstream targets. We used two independently derived human BMBC cell systems (MB-231BR and MB-231BR3), which possess distinct cellular morphologies and properties. Highly aggressive spindle-shaped 231BR3 cells changed to a round cell morphology associated with expression of the small GTPase guanine nucleotide exchange factor-H1 (GEF-H1). We showed that GEF-H1 is a new component of the SDC4 signaling complex in BMBC cells. Treatment with heparanase resulted in regulation of the SDC4/protein kinase C α axis while maintaining a constitutive GEF-H1 level. Third, GEF-H1 knockdown followed by cell exposure to heparanase caused a significant regulation of activities of Rac1 and RhoA, which are GEF-H1 targets and fundamental effectors in cell plasticity control. Fourth, L-heparanase augmented expression of β1 integrin in BMBC cells and of vascular cell adhesion molecule 1 (VCAM1; the major β1 integrin receptor) in human brain microvascular endothelial cells. Finally, using a newly developed blood–brain barrier in vitro model, we show that BMBC cell transmigration was significantly reduced in GEF-H1 knockdown cells. These findings implicate heparanase in mechanisms of cytoskeletal dynamics and in the cross-talk between tumor cells and vascular brain endothelium. They are of relevance because they elucidate molecular events in the initial steps leading to BMBC onset and capturing distinct roles of latent and active heparanase in the brain microenvironment. Mol Cancer Res; 10(6); 689–702. ©2012 AACR.