bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contributions of the Avian Influenza Virus HA, NA, and M2 Surface Proteins to the Induction of Neutralizing Antibodies and Protective Immunity
Authors: Nayak Baibaswata , Kumar Sachin , DiNapoli Joshua M. , Paldurai Anandan , Perez Daniel R. , Collins Peter L. , Samal Siba K. 
Published: December 2009

ABSTRACT
Highly pathogenic avian influenza virus (HPAIV) subtype H5N1 causes severe disease and mortality in poultry. Increased transmission of H5N1 HPAIV from birds to humans is a serious threat to public health. We evaluated the individual contributions of each of the three HPAIV surface proteins, namely, the hemagglutinin (HA), the neuraminidase (NA), and the M2 proteins, to the induction of HPAIV-neutralizing serum antibodies and protective immunity in chickens. Using reverse genetics, three recombinant Newcastle disease viruses (rNDVs) were engineered, each expressing the HA, NA, or M2 protein of H5N1 HPAIV. Chickens were immunized with NDVs expressing a single antigen (HA, NA, and M2), two antigens (HA+NA, HA+M2, and NA+M2), or three antigens (HA+NA+M2). Immunization with HA or NA induced high titers of HPAIV-neutralizing serum antibodies, with the response to HA being greater, thus identifying HA and NA as independent neutralization antigens. M2 did not induce a detectable neutralizing serum antibody response, and inclusion of M2 with HA or NA reduced the magnitude of the response. Immunization with HA alone or in combination with NA induced complete protection against HPAIV challenge. Immunization with NA alone or in combination with M2 did not prevent death following challenge, but extended the time period before death. Immunization with M2 alone had no effect on morbidity or mortality. Thus, there was no indication that M2 is immunogenic or protective. Furthermore, inclusion of NA in addition to HA in a vaccine preparation for chickens may not enhance the high level of protection provided by HA.
A Human Cytomegalovirus gO-Null Mutant Fails To Incorporate gH/gL into the Virion Envelope and Is Unable To Enter Fibroblasts and Epithelial and Endothelial Cells
Authors: Wille Paul T. , Knoche Amber J. , Nelson Jay A. , Jarvis Michael A. , Johnson David C. 
Published: December 2009

ABSTRACT
Human cytomegalovirus (HCMV) depends upon a five-protein complex, gH/gL/UL128-131, to enter epithelial and endothelial cells. A separate HCMV gH/gL-containing complex, gH/gL/gO, has been described. Our prevailing model is that gH/gL/UL128-131 is required for entry into biologically important epithelial and endothelial cells and that gH/gL/gO is required for infection of fibroblasts. Genes encoding UL128-131 are rapidly mutated during laboratory propagation of HCMV on fibroblasts, apparently related to selective pressure for the fibroblast entry pathway. Arguing against this model in the accompanying paper by B. J. Ryckman et al. (J. Virol., 84:2597-2609, 2010), we describe evidence that clinical HCMV strain TR expresses a gO molecule that acts to promote endoplasmic reticulum (ER) export of gH/gL and that gO is not stably incorporated into the virus envelope. This was different from results involving fibroblast-adapted HCMV strain AD169, which incorporates gO into the virion envelope. Here, we constructed a TR gO-null mutant, TRΔgO, that replicated to low titers, spread poorly among fibroblasts, but produced normal quantities of extracellular virus particles. TRΔgO particles released from fibroblasts failed to infect fibroblasts and epithelial and endothelial cells, but the chemical fusogen polyethylene glycol (PEG) could partially overcome defects in infection. Therefore, TRΔgO is defective for entry into all three cell types. Defects in entry were explained by observations showing that TRΔgO incorporated about 5% of the quantities of gH/gL in extracellular virus particles compared with that in wild-type virions. Although TRΔgO particles could not enter cells, cell-to-cell spread involving epithelial and endothelial cells was increased relative to TR, apparently resulting from increased quantities of gH/gL/UL128-131 in virions. Together, our data suggest that TR gO acts as a chaperone to promote ER export and the incorporation of gH/gL complexes into the HCMV envelope. Moreover, these data suggest that it is gH/gL, and not gH/gL/gO, that is present in virions and is required for infection of fibroblasts and epithelial and endothelial cells. Our observations that both gH/gL and gH/gL/UL128-131 are required for entry into epithelial/endothelial cells differ from models for other beta- and gammaherpesviruses that use one of two different gH/gL complexes to enter different cells.
The Janus-Face of New Reproductive Technologies: Escaping the Polarized Debate
Authors: Widdows Heather 
Published: December 2009

AbstractReproduction is held by some to be a divine gift, and by others to be a matter of reproductive rights. The first can leave infertile couples feeling unfulfilled and ‘unblessed’ and the second can be seen as dehumanizing. Yet, despite these vastly divergent understandings, public theology has given little guidance on the use of reproductive technologies and little consideration to their effect on women in particular. This article will interrogate the fault line in feminist thinking—between those who view reproduction as a source of disempowerment and those who view it as empowering—and explore how the debate has developed with the introduction of New Reproductive Technologies (NRTs). It will track the original debate about reproduction in first and second wave feminism. Then, it will consider how this debate has changed with the advent of NRTs. The final section will turn to feminist theology and its surprising lack of contribution to this debate. It will conclude by seeking possible ways forward, identifying resources, in the original feminist debate and in feminist theology, that could usefully be brought into conversation with public theology in order to address this core feminist concern.
Macrophage activation in exacerbated COPD with and without community-acquired pneumonia
Authors: Gutierrez P. , Closa D. , Piñer R. , Bulbena O. , Menéndez R. , Torres A. 
Published: December 2009

In large series of nonresponding community-acquired pneumonia (CAP) patients, chronic obstructive pulmonary disease (COPD) was observed to be a protective factor for nonresponse to initial antibiotics. This intriguing fact may be linked to changes in the phenotype of inflammatory cells and, in particular, to the induction of classical-M1 or alternative-M2 activation of macrophages, which result in different inflammatory profiles.We evaluated the effect of sputum obtained from patients with acute exacerbation of COPD (AECOPD), CAP and COPD+CAP on the phenotypic changes in macrophages. Human THP1 cells differentiated to macrophages were incubated with sputum from patients with AECOPD, CAP or COPD+CAP, and expression of tumour necrosis factor-α, interleukin-6, mannose receptor and arginase was measured to evaluate the phenotype acquired by macrophages. We found that sputum from CAP patients induced the M1 phenotype and that from AECOPD patients induced an M2-like phenotype. Sputum from CAP+COPD patients did not present a clear M1 or M2 phenotype.These results indicate that the microenvironment in the lung modulates the activation of macrophages, resulting in different phenotypes in AECOPD, CAP and COPD+CAP patients. This different type of activation induces different inflammatory responses and may be involved in the different outcome observed when COPD and CAP present simultaneously.
The malate synthase of Paracoccidioides brasiliensisis a linked surface protein that behaves as an anchorless adhesin
Authors: da Silva Neto Benedito Rodrigues , de Fátima da Silva Julhiany , Mendes-Giannini Maria José Soares , Lenzi Henrique Leonel , de Almeida Soares Célia Maria , Pereira Maristela 
Published: December 2009

Abstract

Background
The pathogenic fungus Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM). This is a pulmonary mycosis acquired by inhalation of fungal airborne propagules that can disseminate to several organs and tissues leading to a severe form of the disease. Adhesion and invasion to host cells are essential steps involved in the internalization and dissemination of pathogens. Inside the host, P. brasiliensis may use the glyoxylate cycle for intracellular survival.

Results
Here, we provide evidence that the malate synthase of P. brasiliensis (PbMLS) is located on the fungal cell surface, and is secreted. PbMLS was overexpressed in Escherichia coli, and polyclonal antibody was obtained against this protein. By using Confocal Laser Scanning Microscopy, PbMLS was detected in the cytoplasm and in the cell wall of the mother, but mainly of budding cells of the P. brasiliensis yeast phase. PbMLSr and its respective polyclonal antibody produced against this protein inhibited the interaction of P. brasiliensis with in vitro cultured epithelial cells A549.

Conclusion
These observations indicated that cell wall-associated PbMLS could be mediating the binding of fungal cells to the host, thus contributing to the adhesion of fungus to host tissues and to the dissemination of infection, behaving as an anchorless adhesin.
Quantitative mass spectrometry of TATA binding protein-containing complexes and subunit phosphorylations during the cell cycle
Authors: Pijnappel WWM Pim , Kolkman Annemieke , Baltissen Marijke PA , Heck Albert JR , Timmers HT Marc 
Published: December 2009

Abstract

Background
Progression through the cell cycle is accompanied by tightly controlled regulation of transcription. On one hand, a subset of genes is expressed in a cell cycle-dependent manner. On the other hand, a general inhibition of transcription occurs during mitosis.
Genetic and genome-wide studies suggest cell cycle regulation at the level of transcription initiation by protein complexes containing the common DNA-binding subunit TATA binding protein (TBP). TBP is a key player in regulating transcription by all three nuclear RNA polymerases. It forms at least four distinct protein complexes with TBP-associated factors (TAFs): SL1, B-TFIID, TFIID, and TFIIIB. Some TAFs are known to remain associated with TBP during the cell cycle. Here we analyze all TAFs and their phosphorylation status during the cell cycle using a quantitative mass spectrometry approach.

Results
TBP protein complexes present in human cells at the G2/M and G1/S transitions were analyzed by combining affinity purification with quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture (SILAC). Phosphorylations were mapped and quantified after enrichment of tryptic peptides by titanium dioxide. This revealed that subunit stoichiometries of TBP complexes remained intact, but their relative abundances in nuclear extracts changed during the cell cycle. Several novel phosphorylations were detected on subunits of the TBP complexes TFIID and SL1. G2/M-specific phosphorylations were detected on TAF1, TAF4, TAF7, and TAFI41/TAF1D, and G1/S-specific dephosphorylations were detected on TAF3. Many phosphorylated residues were evolutionary conserved from human to zebrafish and/or drosophila, and were present in conserved regions suggesting important regulatory functions.

Conclusions
This study provides the first quantitative proteomic analysis of human TBP containing protein complexes at the G2/M and G1/S transitions, and identifies new cell cycle-dependent phosphorylations on TAFs present in their protein complex. We speculate that phosphorylation of complex-specific subunits may be involved in regulating the activities of TBP protein complexes during the cell cycle.
Planning health behaviour change: Comparing the behavioural influence of two types of self‐regulatory planning
Authors: van Osch Liesbeth , Reubsaet Astrid , Lechner Lilian , Beenackers Mariëlle , Candel Math , de Vries Hein 
Published: December 2009

ObjectivesRecent efforts in health psychology to bridge the gap between individuals' intentions and behaviour have centered on the influence of planning strategies. This study investigated the impact of two commonly used types of self‐regulatory planning in the prediction of health promoting behaviour.DesignThis study employed a prospective longitudinal design. Three measurements were implemented in order to assess associations between various socio‐cognitive determinants, planning, and health behaviour.MethodsStructural equation modelling (N=572) was used to compare the value of preparatory planning, i.e. the planning of strategies and preparatory actions towards a goal behaviour, and implemental planning, i.e. the planning of when, where, and how to perform a goal behaviour, in the prediction of fruit consumption.ResultsBoth preparatory planning (ß=0.21; p<.001) and implemental planning (ß=0.13; p<.01) were significant predictors of fruit consumption, over and above the influence of motivational factors. Comparison of differences in explained variance (ΔR2) indicated that the contribution of preparatory planning was larger than that of implemental planning (z=2.19; p<.05). Implemental planning did not contribute to the prediction of fruit consumption over and above the influence of preparatory planning when tested simultaneously.ConclusionsThe results provide a first indication that the planning of strategic preparatory actions may be more influential in predicting health behaviour than implemental planning, focusing on when, where, and how to enact goal‐directed behaviour. Implications of the results and suggestions for future research are outlined.
The Experiences and Needs of People Who Cease Driving After Stroke
Authors: Liddle Jacki , Turpin Merrill , McKenna Kryss , Kubus Tara , Lambley Sonia , McCaffrey Katherine 
Published: December 2009

AbstractDriving cessation can result in a range of negative consequences, including impacts on identity, mood, and life satisfaction. The aims of this study were to explore the needs and experiences of people who cease driving following a stroke, with the aim of informing clinical practice.Method:Using a qualitative phenomenological approach, semi-structured, audiotaped interviews were conducted to gain an understanding of the needs and experiences of 24 participants (17 male, 7 female, mean of 5.5 years post driving cessation) who had ceased driving following a stroke.Results:After constant comparative analysis, four themes emerged from the data. These were labelled ‘life without driving’, ‘key times of need’, ‘alternatives and other ways’, and ‘carer support and assistance’. Most participants found stopping driving after their stroke to be a sudden, unexpected and intense experience and raised issues, including the loss of numerous life-roles, challenges associated with arranging alternative transport, and reliance on carers and the need for more information throughout the process.Conclusion:Individuals who cease driving following a stroke have unmet needs and difficult experiences throughout the process. Key times of particular need have been identified in this study. These findings have important implications for health professionals that include providing more information and support with driving cessation and alternatives to driving.
Supporting the Needs of Young Adults With Acquired Brain Injury During Transition From Hospital to Home: The Queensland Service Provider Perspective
Authors: Cornwell Petrea , Fleming Jennifer , Fisher Annette , Kendall Melissa , Ownsworth Tamara , Turner Benjamin 
Published: December 2009

AbstractObjective: To explore the availability and perceived adequacy of service support for younger people with ABI and their families in Queensland during the transition phase from the perspective of service providers. Research Design: A qualitative research design utilising survey-based open-ended questioning. Methods and Procedures: Participants were service provider organisations in Queensland for younger people with aquired brain injury (ABI). A two-part survey was developed for the purpose of the study. The first part of the survey obtained general information regarding client base and service characteristics for each organisation, while the second part was designed to identify gaps in, and barriers and facilitators to service provision. Snowballing recruitment was used with the initial seed point an existing Brain Injury Network. Results: A response rate of 20% was obtained with a total of 12 surveys returned representing seven service providers. Services currently available included rehabilitation, consultancy, education and training, and practical and emotional supports. Existing gaps in, and barriers to service provision were clustered under three key themes: service infrastructure, transition support, and transition context. Some of the facilitators to service provision identified included interagency linkages and financial compensation for injury. Conclusions: Gaps in, and barriers to service provision during the transition phase were identified that could be utilised to develop models of service delivery to improve short- and long-term outcomes for younger people with ABI.
On Parameter Estimation in Hierarchical Credibility
Authors: Belhadj Hassine , Goulet Vincent , Ouellet Tommy 
Published: December 2009

AbstractOne can find in the literature three main sets of estimators for the variance components in the hierarchical credibility model. This paper presents these estimators in a unified notation, studies some of their properties important for numerical evaluation and compares their relative performance by simulation. The paper also demonstrates how function cm of the R package actuar can be used to fit hierarchical models to insurance data.
A Note on Nonparametric Estimation of the CTE
Authors: Ko Bangwon , Russo Ralph P. , Shyamalkumar Nariankadu D. 
Published: December 2009

AbstractThe α-level Conditional Tail Expectation (CTE) of a continuous random variable X is defined as its conditional expectation given the event {X > qα} where qα represents its α-level quantile. It is well known that the empirical CTE (the average of the n (1 – α) largest order statistics in a sample of size n) is a negatively biased estimator of the CTE. This bias vanishes as the sample size increases, but in small samples can be significant. In this article it is shown that an unbiased nonparametric estimator of the CTE does not exist. In addition, the asymptotic behavior of the bias of the empirical CTE is studied, and a closed form expression for its first order term is derived. This expression facilitates the study of the behavior of the empirical CTE with respect to the underlying distribution, and suggests an alternative (to the bootstrap) approach to bias correction. The performance of the resulting estimator is assessed via simulation.
CXCL 9 and CXCL 10 as Sensitive Markers of Disease Activity in Patients with Rheumatoid Arthritis
Authors: KUAN WOON PANG , TAM LAI-SHAN , WONG CHUN-KWOK , KO FANNY W.S. , LI TENA , ZHU TRACY , LI EDMUND K. 
Published: December 2009

Objective.To assess whether serum levels of CC and CXC chemokines correlate with disease activity in patients with rheumatoid arthritis (RA), and to determine whether these effects predict clinical response.Methods.Serum levels of the chemokines CC (CCL2, CCL5) and CXC (CXCL8, CXCL9, CXCL10) were quantified at baseline and after 12 weeks of treatment with disease-modifying antirheumatic drugs or biologic agents in 28 patients using flow cytometry. Serum from 40 healthy individuals was collected for comparison at baseline. Response to treatment was classified according to the European League Against Rheumatism (EULAR) response criteria. Remission of disease was defined as a Disease Activity Score < 2.6.Results.The baseline serum concentrations of CC and CXC chemokines were significantly elevated in patients with active RA compared to healthy controls (p < 0.05) except for CCL2. Significant improvement in all disease activity measurements was observed after 12 weeks of treatment. Seventeen (60.7%) patients achieved good to moderate response based on the EULAR response criteria, and 5 (17.9%) patients achieved remission. The improvement in clinical activity in patients with RA was accompanied by a significant reduction in the serum concentration of CXCL9 and CXCL10 (p < 0.001). A significant reduction in the serum level of CXCL10 was also observed in the group that achieved EULAR response. Serum concentration of CCL5 remained significantly elevated in patients with RA (n = 5) who achieved remission compared to the healthy controls (p < 0.05).Conclusion.Serum concentration of CXCL9 and CXCL10 may serve as sensitive biomarkers for disease activity in patients with RA.
Human Embryonic Stem Cells Suppress T Cell Responses via Arginase I-Dependent Mechanism
Authors: Yachimovich-Cohen Nurit , Even-Ram Sharona , Shufaro Yoel , Rachmilewitz Jacob , Reubinoff Benjamin 
Published: December 2009

Abstract
Human embryonic stem cells (hESCs) can proliferate extensively in culture and give rise to progeny of the three germ layers. Several reports suggested that mouse and hESCs may attenuate immune responses. In this study, we focused on the mechanism by which hESCs inhibit T cell responses. Using coculture experiments, we demonstrate that hESCs inhibit cytokine secretion and T cell proliferation in response to potent T cell activators. Furthermore, we show that hESCs downmodulate the TCR-associated CD3-ζ chain. These effects are maintained when hESCs are replaced by their conditioned media and can be restored by the addition of l-arginine to hESC-conditioned media or by treatment of hESCs with a specific arginase inhibitor. Moreover, we show arginase-I expression and activity in hESCs. We further demonstrate that mouse ESCs (mESCs) similarly inhibit T cell activation via arginase I, suggesting an evolutionary conserved mechanism of T cell suppression by ESCs. In addition, we demonstrate that arginase I expression is not limited to ESCs in culture, but can also be detected in the inner cell mass and the trophectoderm of preimplantation mouse embryos and hESC-derived trophectoderm cells. Finally, T cells infiltrating ESC-derived teratomas have significantly lower levels of CD3-ζ chain. Collectively, the data indicate a role for ESC-arginase I activity in the attenuation of T cell activation.