bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nuclear Localization of Tegument-Delivered pp71 in Human Cytomegalovirus-Infected Cells Is Facilitated by One or More Factors Present in Terminally Differentiated Fibroblasts
Authors: Penkert Rhiannon R. , Kalejta Robert F. 
Published: August 2010

ABSTRACTHerpesviral virions contain a tegument layer that consists primarily of viral proteins. The delivery of fully functional proteins to infected cells upon virion envelope fusion to the plasma membrane allows herpesviruses to modulate cellular activities prior to viral gene expression. Certain tegument proteins can also regulate viral processes. For example, the pp71 tegument protein encoded by the UL82 gene of human cytomegalovirus (HCMV) stimulates viral immediate early (IE) gene expression and thus acts to initiate the productive lytic infectious cycle. In terminally differentiated fibroblasts infected with HCMV, tegument-delivered pp71 traffics to the nucleus and degrades the cellular transcriptional corepressor Daxx to initiate viral IE gene expression and lytic replication. However, when HCMV infects incompletely differentiated cells, tegument-delivered pp71 remains in the cytoplasm, allowing the nucleus-localized Daxx protein to silence viral IE gene expression and promote the establishment of a latent infection in certain cell types. We sought to determine whether undifferentiated cells block the trafficking of tegument-delivered pp71 to the nucleus or whether differentiated cells facilitate the nuclear transport of tegument-delivered pp71. Heterogenous cell fusion experiments demonstrated that tegument-delivered pp71 found in the cytoplasm of undifferentiated NT2 cells could be driven into the nucleus by one or more factors provided by fully differentiated fibroblasts. Our data raise the intriguing possibility that latency is the default program launched by HCMV upon viral entry into cells and that lytic infection is initiated only in certain (differentiated) cells that can facilitate the delivery of incoming pp71 to the nucleus.
Identification of Alpha Interferon-Induced Genes Associated with Antiviral Activity in Daudi Cells and Characterization of IFIT3 as a Novel Antiviral Gene
Authors: Schmeisser H. , Mejido J. , Balinsky C. A. , Morrow A. N. , Clark C. R. , Zhao T. , Zoon K. C. 
Published: August 2010

ABSTRACTA novel assay was developed for Daudi cells in which the antiviral (AV) and antiproliferative (AP) activities of interferon (IFN) can be measured simultaneously. Using this novel assay, conditions allowing IFN AV protection but no growth inhibition were identified and selected. Daudi cells were treated under these conditions, and gene expression microarray analyses were performed. The results of the analysis identified 25 genes associated with IFN-α AV activity. Upregulation of 23 IFN-induced genes was confirmed by using reverse transcription-PCR. Of 25 gene products, 17 were detected by Western blotting at 24 h. Of the 25 genes, 10 have not been previously linked to AV activity of IFN-α. The most upregulated gene was IFIT3 (for IFN-induced protein with tetratricopeptide repeats 3). The results from antibody neutralizing experiments suggested an association of the identified genes with IFN-α AV activity. This association was strengthened by results from IFIT3-small interfering RNA transfection experiments showing decreased expression of IFIT3 and a reduction in the AV activity induced by IFN-α. Overexpression of IFIT3 resulted in a decrease of virus titer. Transcription of AV genes after the treatment of cells with higher concentrations of IFN having an AP effect on Daudi cells suggested pleiotropic functions of identified gene products.
The Human Papillomavirus Type 16 E5 Oncoprotein Inhibits Epidermal Growth Factor Trafficking Independently of Endosome Acidification
Authors: Suprynowicz Frank A. , Krawczyk Ewa , Hebert Jess D. , Sudarshan Sawali R. , Simic Vera , Kamonjoh Christopher M. , Schlegel Richard 
Published: August 2010

ABSTRACTThe human papillomavirus type 16 E5 oncoprotein (16E5) enhances acute, ligand-dependent activation of the epidermal growth factor receptor (EGFR) and concomitantly alkalinizes endosomes, presumably by binding to the 16-kDa “c” subunit of the V-ATPase proton pump (16K) and inhibiting V-ATPase function. However, the relationship between 16K binding, endosome alkalinization, and altered EGFR signaling remains unclear. Using an antibody that we generated against 16K, we found that 16E5 associated with only a small fraction of endogenous 16K in keratinocytes, suggesting that it was unlikely that E5 could significantly affect V-ATPase function by direct inhibition. Nevertheless, E5 inhibited the acidification of endosomes, as determined by a new assay using a biologically active, pH-sensitive fluorescent EGF conjugate. Since we also found that 16E5 did not alter cell surface EGF binding, the number of EGFRs on the cell surface, or the endocytosis of prebound EGF, we postulated that it might be blocking the fusion of early endosomes with acidified vesicles. Our studies with pH-sensitive and -insensitive fluorescent EGF conjugates and fluorescent dextran confirmed that E5 prevented endosome maturation (acidification and enlargement) by inhibiting endosome fusion. The E5-dependent defect in vesicle fusion was not due to detectable disruption of actin, tubulin, vimentin, or cytokeratin filaments, suggesting that membrane fusion was being directly affected rather than vesicle transport. Perhaps most importantly, while bafilomycin A1(like E5) binds to 16K and inhibits endosome acidification, it did not mimic the ability of E5 to inhibit endosome enlargement or the trafficking of EGF. Thus, 16E5 alters EGF endocytic trafficking via a pH-independent inhibition of vesicle fusion.
Mononucleosis and Antigen-Driven T Cell Responses Have Different Requirements for Interleukin-2 Signaling in Murine Gammaherpesvirus Infection
Authors: Molloy Michael , Zhang Weijun , Usherwood Edward 
Published: August 2010

ABSTRACTInterleukin-2 (IL-2) has been implicated as being necessary for the optimal formation of primary CD8+T cell responses against various pathogens. Here we have examined the role that IL-2 signaling plays in several aspects of a CD8+T cell response against murine gammaherpesvirus 68 (MHV-68). Exposure to MHV-68 causes a persistent infection, along with infectious mononucleosis, providing a model for studying these processes in mice. Our study indicates that CD25 is necessary for optimal expansion of the antigen-specific CD8+T cell response but not for the long-term memory response. Contrastingly, IL-2 signaling through CD25 is absolutely required for CD8+T cell mononucleosis.
Crystallographic Structure of Porcine Adenovirus Type 4 Fiber Head and Galectin Domains
Authors: Guardado-Calvo Pablo , Muñoz Eva M. , Llamas-Saiz Antonio L. , Fox Gavin C. , Kahn Richard , Curiel David T. , Glasgow Joel N. , van Raaij Mark J. 
Published: August 2010

ABSTRACT

Adenovirus isolate NADC-1, a strain of porcine adenovirus type 4, has a fiber containing an N-terminal virus attachment region, shaft and head domains, and a C-terminal galectin domain connected to the head by an RGD-containing sequence. The crystal structure of the head domain is similar to previously solved adenovirus fiber head domains, but specific residues for binding the coxsackievirus and adenovirus receptor (CAR), CD46, or sialic acid are not conserved. The structure of the galectin domain reveals an interaction interface between its two carbohydrate recognition domains, locating both sugar binding sites face to face. Sequence evidence suggests other tandem-repeat galectins have the same arrangement. We show that the galectin domain binds carbohydrates containing lactose and
N
-acetyl-lactosamine units, and we present structures of the galectin domain with lactose,
N
-acetyl-lactosamine, 3-aminopropyl-lacto-
N
-neotetraose, and 2-aminoethyl-tri(
N
-acetyl-lactosamine), confirming the domain as a bona fide galectin domain.
Low-Dose Mucosal Simian Immunodeficiency Virus Infection Restricts Early Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys
Authors: Liu Jinyan , Keele Brandon F. , Li Hui , Keating Sheila , Norris Philip J. , Carville Angela , Mansfield Keith G. , Tomaras Georgia D. , Haynes Barton F. , Kolodkin-Gal Dror , Letvin Norman L. , Hahn Beatrice H. , Shaw George M. , Barouch Dan H. 
Published: August 2010

ABSTRACT
Defining the earliest virologic events following human immunodeficiency virus type 1 (HIV-1) transmission may be critical for the design of vaccine strategies aimed at blocking acquisition of HIV-1 infection. In particular, the length of the eclipse phase and the number of transmitted virus variants may define the window in which a prophylactic vaccine must act. Here we show that the dose of the virus inoculum affects these key virologic parameters following intrarectal simian immunodeficiency virus (SIV) infection of rhesus monkeys. Low-dose SIV infection resulted in a lengthened eclipse phase, fewer transmitted virus variants, and decreased innate immune activation compared with these parameters in high-dose SIV infection. These data suggest a mechanism by which it may be considerably easier for a vaccine to protect against low-risk HIV-1 transmission than against high-risk HIV-1 transmission. These findings have implications for the design and interpretation of HIV-1 vaccine efficacy studies.
Mann Type Implicit Iteration Approximation for Multivalued Mappings in Banach Spaces
Authors: He Huimin , Liu Sanyang , Chen Rudong 
Published: August 2010

AbstractLet "Equation missing" be a nonempty compact convex subset of a uniformly convex Banach space "Equation missing" and let"Equation missing" be a multivalued nonexpansive mapping. For the implicit iterates "Equation missing", "Equation missing", "Equation missing", "Equation missing". We proved that "Equation missing" converges strongly to a fixed point of "Equation missing" under some suitable conditions. Our results extended corresponding ones and revised a gap in the work of Panyanak (2007).
HLA-DRB1*1501 intensifies the impact of IL-6 promoter polymorphism on the susceptibility to multiple sclerosis in an Iranian population
Authors: Shahbazi M. , Ebadi H. , Fathi D. , Roshandel D. , Mohamadhosseni M. , Tahmasebi A. , Shahbazi S. , Zamani M. , Rashidbaghan A. 
Published: August 2010

Background: The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system. It is well documented that amount of IL-6 is increased in serum, cerebrospinal fluid and central nervous system lesions of patients with multiple sclerosis. A single nucleotide polymorphism at position -174 in the IL-6 gene promotor appears to influence IL-6 expression. Recently, several researchers have focused on HLA-DRB alleles, specifically HLA-DRB1*1501, as a potential risk allele in the pathogenesis of multiple sclerosis. Objective: To investigate the possible influence of IL-6/-174 polymorphisms on susceptibility to multiple sclerosis and its integration with HLA-DRB1*1501. Genomic DNA was extracted from whole blood of 345 patients with multiple sclerosis and 426 control subjects. Method: The SSP-PCR method was used to determine genotypes and Fisher’s exact test was applied to determine differences between groups. HLA-DRB1*1501 was observed more frequently among multiple sclerosis patients compared with healthy subjects (45% and 34%, respectively; OR = 1.6, 95% CI = 1.2—2.2, p = 0.0018). At the IL-6/-174 position, the G allele had higher frequency among multiple sclerosis patients compared with controls (77% and 70%, respectively; OR = 1.4, 95% CI = 1.1—1.8, p = 0.0038). This difference was more significant among HLA-DRB1*1501-positive patients and controls (81% and 67%, respectively; OR = 1.9, 95% CI = 1.5—2.5, p < 0.0001). Results: Our results have shown that the G allele at the IL-6/-174 promoter polymorphism may be associated with development of multiple sclerosis in this population, and may be strengthened by HLA-DRB1*1501. Conclusions: We suggest more studies to confirm these results in other populations.
Serum antibodies to conformational and linear epitopes of myelin oligodendrocyte glycoprotein are not elevated in the preclinical phase of multiple sclerosis
Authors: Chan A. , Decard BF , Franke C. , Grummel V. , Zhou D. , Schottstedt V. , Toyka KV , Hemmer B. , Gold R. 
Published: August 2010

Background: The proposed predictive value of serum anti-myelin antibodies for the development of multiple sclerosis after a first clinically isolated syndrome was recently challenged. Objective: To investigate myelin autoantibodies before first disease manifestation using different detection methods. Methods: Patients with multiple sclerosis who had donated blood at a time prior to development of clinically isolated syndrome were identified via the German National Multiple Sclerosis Society. Control sera were obtained from age- and gender-matched blood donors. IgG-/IgM-antibodies against the extracellular part of native, cell surface-expressed myelin oligodendrocyte glycoprotein were detected by flow cytometry. Antibodies against linear epitopes were identified by immunoblot using recombinant myelin oligodendrocyte glycoprotein (aa1-125) and human myelin basic protein preparations. Results: Fifty eight serum samples from 25 patients covering an interval of 7.3 years—2 months prior to disease onset were available. Longitudinal investigations were performed in 19 patients (2—14 samples per patient, 7 years—2 months prior to disease onset). No significant differences in the prevalence or titres of anti-myelin antibodies were detected between sera of preclinical individuals and healthy donors by either flow cytometry or immunoblot. There was no correlation between interval before clinically isolated syndrome and autoantibody status. Occurrence of antibodies was not associated with symptomatology/severity of clinically isolated syndrome. Conclusion: Neither anti-myelin autoantibodies against cell surface-expressed native myelin oligodendrocyte glycoprotein nor against linear epitopes have a predictive or discriminative role during the preclinical disease phase for developing clinically isolated syndrome or multiple sclerosis later in life.
Improving the translational hit of experimental treatments in multiple sclerosis
Authors: Vesterinen Hanna M , Sena Emily S , ffrench-Constant Charles , Williams Anna , Chandran Siddharthan , Macleod Malcolm R 
Published: August 2010

Background: In other neurological diseases, the failure to translate pre-clinical findings to effective clinical treatments has been partially attributed to bias introduced by shortcomings in the design of animal experiments. Objectives: Here we evaluate published studies of interventions in animal models of multiple sclerosis for methodological design and quality and to identify candidate interventions with the best evidence of efficacy. Methods: A systematic review of the literature describing experiments testing the effectiveness of interventions in animal models of multiple sclerosis was carried out. Data were extracted for reported study quality and design and for neurobehavioural outcome. Weighted mean difference meta-analysis was used to provide summary estimates of the efficacy for drugs where this was reported in five or more publications. Results: The use of a drug in a pre-clinical multiple sclerosis model was reported in 1152 publications, of which 1117 were experimental autoimmune encephalomyelitis (EAE). For 36 interventions analysed in greater detail, neurobehavioural score was improved by 39.6% (95% CI 34.9—44.2%, p < 0.001). However, few studies reported measures to reduce bias, and those reporting randomization or blinding found significantly smaller effect sizes. Conclusions: EAE has proven to be a valuable model in elucidating pathogenesis as well as identifying candidate therapies for multiple sclerosis. However, there is an inconsistent application of measures to limit bias that could be addressed by adopting methodological best practice in study design. Our analysis provides an estimate of sample size required for different levels of power in future studies and suggests a number of interventions for which there are substantial animal data supporting efficacy.
mab-31 and the TGF-β pathway act in the ray lineage to pattern C. elegansmale sensory rays
Authors: Wong Yan-Fung , Sheng Qing , Chung Janet WL , Chan Jacky KF , Chow King L 
Published: August 2010

Abstract

Background

C. elegans TGF-β-like Sma/Mab signaling pathway regulates both body size and sensory ray patterning. Most of the components in this pathway were initially identified by genetic screens based on the small body phenotype, and many of these mutants display sensory ray patterning defect. At the cellular level, little is known about how and where these components work although ray structural cell has been implicated as one of the targets. Based on the specific ray patterning abnormality, we aim to identify by RNAi approach additional components that function specifically in the ray lineage to elucidate the regulatory role of TGF-β signaling in ray differentiation.

Result
We report here the characterization of a new member of the Sma/Mab pathway, mab-31, recovered from a genome-wide RNAi screen. mab-31 mutants showed ray cell cluster patterning defect and mis-specification of the ray identity. mab-31 encodes a nuclear protein expressed in descendants of ray precursor cells impacting on the ray cell's clustering properties, orientation of cell division plane, and fusion of structural cells. Genetic experiments also establish its relationship with other Sma/Mab pathway components and transcription factors acting upstream and downstream of the signaling event.

Conclusion

mab-31 function is indispensable in Sma/Mab signal recipient cells during sensory rays specification. Both mab-31 and sma-6 are required in ray lineage at the late larval stages. They act upstream of C. elegans Pax-6 homolog and repress its function. These findings suggested mab-31 is a key factor that can integrate TFG-β signals in male sensory ray lineage to define organ identity.
The impact of attrition on the representativeness of cohort studies of older people
Authors: Brilleman Samuel L , Pachana Nancy A , Dobson Annette J 
Published: August 2010

Abstract

Background
There are well-established risk factors, such as lower education, for attrition of study participants. Consequently, the representativeness of the cohort in a longitudinal study may deteriorate over time. Death is a common form of attrition in cohort studies of older people. The aim of this paper is to examine the effects of death and other forms of attrition on risk factor prevalence in the study cohort and the target population over time.

Methods
Differential associations between a risk factor and death and non-death attrition are considered under various hypothetical conditions. Empirical data from the Australian Longitudinal Study on Women's Health (ALSWH) for participants born in 1921-26 are used to identify associations which occur in practice, and national cross-sectional data from Australian Censuses and National Health Surveys are used to illustrate the evolution of bias over approximately ten years.

Results
The hypothetical situations illustrate how death and other attrition can theoretically affect changes in bias over time. Between 1996 and 2008, 28.4% of ALSWH participants died, 16.5% withdrew and 10.4% were lost to follow up. There were differential associations with various risk factors, for example, non-English speaking country of birth was associated with non-death attrition but not death whereas being underweight (body mass index < 18.5) was associated with death but not other forms of attrition. Compared to national data, underrepresentation of women with non-English speaking country of birth increased from 3.9% to 7.2% and over-representation of current and ex-smoking increased from 2.6% to 5.8%.

Conclusions
Deaths occur in both the target population and study cohort, while other forms of attrition occur only in the study cohort. Therefore non-death attrition may cause greater bias than death in longitudinal studies. However although more than a quarter of the oldest participants in the ALSWH died in the 12 years following recruitment, differences from the national population changed only slightly.
A systematic review of randomized controlled trials exploring the effect of immunomodulative interventions on infection, organ failure, and mortality in trauma patients
Authors: Spruijt Nicole E , Visser Tjaakje , Leenen Luke PH 
Published: August 2010

Abstract
Introduction
Following trauma, patients may suffer an overwhelming pro-inflammatory response and immune paralysis resulting in infection and multiple organ failure (MOF). Various potentially immunomodulative interventions have been tested. The objective of this study is to systematically review the randomized controlled trials (RCTs) that investigate the effect of potentially immunomodulative interventions in comparison to a placebo or standard therapy on infection, MOF, and mortality in trauma patients.

Methods
A computerized search of MEDLINE, the Cochrane CENTRAL Register of Controlled Trials, and EMBASE yielded 502 studies, of which 18 unique RCTs were deemed relevant for this study. The methodological quality of these RCTs was assessed using a critical appraisal checklist for therapy articles from the Centre for Evidence Based Medicine. The effects of the test interventions on infection, MOF, and mortality rates and inflammatory parameters relative to the controls were recorded.

Results
In most studies, the inflammatory parameters differed significantly between the test and control groups. However, significant changes in infection, MOF, and mortality rates were only measured in studies testing immunoglobulin, IFN-γ, and glucan.

Conclusions
Based on level 1b and 2b studies, administration of immunoglobulin, IFN-γ, or glucan have shown the most promising results to improve the outcome of trauma patients.
Modulation of human neutrophil survival and antigen expression by activated CD4+ and CD8+ T cells
Authors: Pelletier Martin , Micheletti Alessandra , Cassatella Marco A 
Published: August 2010

Abstract
CD8+ T cells modulate neutrophil apoptosis and surface marker expression via TNF-α, IFN-γ and GM-CSF, while CD4+ T cells effects involve IFN-γ and GM-CSF.
Neutrophils and T cells often co-infiltrate pathological tissues, which suggests that these 2 cell types may interact with each other. Over the years, in vitro studies have demonstrated that neutrophils and T cells are capable of modulating each otherˈs responses. However, few studies have examined the cross-talk between human neutrophils and CD8+ T cells, although murine models clearly show the critical role of their interaction in bacterial infections and cancer. Herein, we evaluated the interaction between human neutrophils and CD8+ T cells in a coculture system using highly purified cell preparations and compared the responses to ones from cocultures of neutrophils and CD4+ T cells. We report that anti-CD3-activated CD4+ and more potently, anti-CD3-activated CD8+ T cells modulate apoptosis and expression of activation markers by neutrophils, and neutrophils have no or little effect on T cell survival, expression of surface markers, and cytokine release. The observed effects of CD8+ T cells on neutrophils were mainly attributable to the release of TNF-α, IFN-γ, and GM-CSF, and the effects of CD4+ T cells involved IFN-γ and GM-CSF production. This study expands our knowledge of the molecular bases, whereby human CD4+ and CD8+ T cells modulate neutrophil survival and antigen expression.