bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Specific Innate Immune Responses in Herpes Simplex Virus Infection of the Central Nervous System
Authors: Wang Jennifer P. , Bowen Glennice N. , Zhou Shenghua , Cerny Anna , Zacharia An , Knipe David M. , Finberg Robert W. , Kurt-Jones Evelyn A. 
Published: December 2011

ABSTRACT
Herpes simplex virus 1 (HSV-1) causes a spectrum of disease, including herpes labialis, herpes keratitis, and herpes encephalitis, which can be lethal. Viral recognition by pattern recognition receptors plays a central role in cytokine production and in the generation of antiviral immunity. The relative contributions of different Toll-like receptors (TLRs) in the innate immune response during central nervous system infection with HSV-1 have not been fully characterized. In this study, we investigate the roles of TLR2, TLR9, UNC93B1, and the type I interferon (IFN) receptor in a murine model of HSV-1 encephalitis. TLR2 is responsible for detrimental inflammatory cytokine production following intracranial infection with HSV-1, and the absence of TLR2 expression leads to increased survival in mice. We prove that inflammatory cytokine production by microglial cells, astrocytes, neutrophils, and monocytes is mediated predominantly by TLR2. We also demonstrate that type I IFNs are absolutely required for survival following intracranial HSV-1 infection, as mice lacking the type I IFN receptor succumb rapidly following infection and have high levels of HSV in the brain. However, the absence of TLR9 does not impact survival, type I IFN levels, or viral replication in the brain following infection. The absence of UNC93B1 leads to a survival disadvantage but does not impact viral replication or type I IFN levels in the brain in HSV-1-infected mice. These results illustrate the complex but important roles that innate immune receptors play in host responses to HSV-1 during infection of the central nervous system.
Identification of RNA Helicase A as a Cellular Factor That Interacts with Influenza A Virus NS1 Protein and Its Role in the Virus Life Cycle
Authors: Lin Li , Li Yang , Pyo Hyun-Mi , Lu Xinya , Raman Sathya N. Thulasi , Liu Qiang , Brown Earl G. , Zhou Yan 
Published: December 2011

ABSTRACT
Influenza A virus NS1 protein has multiple functions in the infected cell during the virus life cycle. Identification of novel cellular factors that interact with NS1 and understanding their functions in virus infection are of great interest. Recombinant viruses carrying a tagged NS1 are valuable for investigation of interactions between NS1 and cellular factors in the context of virus infection. Here, we report the generation of replication-competent recombinant influenza A viruses bearing a Strep tag in the NS1 protein. Purification of a protein complex associated with Strep-tagged NS1 from virus-infected cells followed by mass spectrometry revealed a number of attractive host factors. Among them, we focused our study on RNA helicase A (RHA) in this report. Through biomedical and functional analyses, we demonstrated that RHA interacts with NS1 in an RNA-dependent manner. Knockdown of RHA resulted in a significant reduction on virus yield and polymerase activity in a minigenome assay. Our cell-free viral genome replication assay showed that viral RNA replication and transcription can be enhanced by addition of RHA, and the enhanced effect of RHA required its ATP-dependent helicase activity. In summary, we established a system to identify cellular factors that interact with NS1 protein during virus infection and furthermore demonstrated that RHA interacts with NS1 and enhances viral replication and transcription.
Naturally Occurring Antibodies That Recognize Linear Epitopes in the Amino Terminus of the Hepatitis C Virus E2 Protein Confer Noninterfering, Additive Neutralization
Authors: Tarr Alexander W. , Urbanowicz Richard A. , Jayaraj Dhanya , Brown Richard J. P. , McKeating Jane A. , Irving William L. , Ball Jonathan K. 
Published: December 2011

ABSTRACT
Chronic hepatitis C virus (HCV) infection can persist even in the presence of a broadly neutralizing antibody response. Various mechanisms that underpin viral persistence have been proposed, and one of the most recently proposed mechanisms is the presence of interfering antibodies that negate neutralizing responses. Specifically, it has been proposed that antibodies targeting broadly neutralizing epitopes located within a region of E2 encompassing residues 412 to 423 can be inhibited by nonneutralizing antibodies binding to a less conserved region encompassing residues 434 to 446. To investigate this phenomenon, we characterized the neutralizing and inhibitory effects of human-derived affinity-purified immunoglobulin fractions and murine monoclonal antibodies and show that antibodies to both regions neutralize HCV pseudoparticle (HCVpp) and cell culture-infectious virus (HCVcc) infection albeit with different breadths and potencies. Epitope mapping revealed the presence of overlapping but distinct epitopes in both regions, which may explain the observed differences in neutralizing phenotypes. Crucially, we failed to demonstrate any inhibition between these two groups of antibodies, suggesting that interference by nonneutralizing antibodies, at least for the region encompassing residues 434 to 446, does not provide a mechanism for HCV persistence in chronically infected individuals.
The Paramyxovirus Fusion Protein C-Terminal Region: Mutagenesis Indicates an Indivisible Protein Unit
Authors: Zokarkar Aarohi , Lamb Robert A. 
Published: December 2011

ABSTRACTParamyxoviruses enter host cells by fusing the viral envelope with a host cell membrane. Fusion is mediated by the viral fusion (F) protein, and it undergoes large irreversible conformational changes to cause membrane merger. The C terminus of PIV5 F contains a membrane-proximal 7-residue external region (MPER), followed by the transmembrane (TM) domain and a 20-residue cytoplasmic tail. To study the sequence requirements of the F protein C terminus for fusion, we constructed chimeras containing the ectodomain of parainfluenza virus 5 F (PIV5 F) and either the MPER, the TM domain, or the cytoplasmic tail of the F proteins of the paramyxoviruses measles virus, mumps virus, Newcastle disease virus, human parainfluenza virus 3, and Nipah virus. The chimeras were expressed, and their ability to cause cell fusion was analyzed. The chimeric proteins were variably expressed at the cell surface. We found that chimeras containing the ectodomain of PIV5 F with the C terminus of other paramyxoviruses were unable to cause cell fusion. Fusion could be restored by decreasing the activation energy of refolding through introduction of a destabilizing mutation (S443P). Replacing individual regions, singly or doubly, in the chimeras with native PIV5 F sequences restored fusion to various degrees, but it did not have an additive effect in restoring activity. Thus, the F protein C terminus may be a specific structure that only functions with its cognate ectodomain. Alanine scanning mutagenesis of MPER indicates that it has a regulatory role in fusion since both hyperfusogenic and hypofusogenic mutations were found.
Glycoproteins D of Equine Herpesvirus Type 1 (EHV-1) and EHV-4 Determine Cellular Tropism Independently of Integrins
Authors: Azab Walid , Osterrieder Nikolaus 
Published: December 2011

ABSTRACT

Equine herpesvirus type 1 (EHV-1) and EHV-4 are genetically and antigenically very similar, but their pathogenic potentials are strikingly different. The differences in pathogenicity between both viruses seem to be reflected in cellular host range: EHV-1 can readily be propagated in many cell types of multiple species, while EHV-4 entry and replication appear to be restricted mainly to equine cells. The clear difference in cellular tropism may well be associated with differences in the gene products involved in virus entry and/or spread from cell to cell. Here we show that (i) most of the EHV-1 permissive cell lines became resistant to EHV-1 expressing EHV-4 glycoprotein D (gD4) and the opposite was observed for EHV-4 harboring EHV-1 gD (gD1). (ii) The absence of integrins did not inhibit entry into and replication of EHV-1 in CHO-K1 or peripheral blood mononuclear cells (PBMC). Furthermore, integrin-negative K562 cells did not acquire the ability to bind to gD1 when αVβ3 integrin was overexpressed. (iii) PBMC could be infected with similar efficiencies by both EHV-1 and EHV-4
in vitro
. (iv) In contrast to results for equine fibroblasts and cells of endothelial or epithelial origin, we were unable to block entry of EHV-1 or EHV-4 into PBMC with antibodies directed against major histocompatibility complex class I (MHC-I), a result that indicates that these viruses utilize a different receptor(s) to infect PBMC. Cumulatively, we provide evidence that efficient EHV-1 and EHV-4 entry is dependent mainly on gD, which can bind to multiple cell surface receptors, and that gD has a defining role with respect to cellular host range of EHV-1 and EHV-4.
Hepatitis C Virus Proteins Inhibit C3 Complement Production
Authors: Mazumdar Budhaditya , Kim Hangeun , Meyer Keith , Bose Sandip K. , Di Bisceglie Adrian M. , Ray Ratna B. , Ray Ranjit 
Published: December 2011

ABSTRACT

The third component of human complement (C3) plays a central role in innate immune function as its activation is required to trigger classical as well as alternative complement pathways. In this study, we have observed that sera from patients chronically infected with hepatitis C virus (HCV) displayed significantly lower C3 levels than sera from healthy individuals. Liver biopsy specimens from the same patients also exhibited lower C3 mRNA expression than liver tissues from healthy donors. C3 mRNA level was reduced in hepatocytes upon infection with cell culture-grown HCV genotype 1a or 2a
in vitro
. Further analysis suggested that HCV core protein displayed a weak repression of C3 promoter activity by downregulating the transcription factor farnesoid X receptor (FXR). On the other hand, HCV NS5A protein strongly downregulated C3 promoter activity at the basal level or in the presence of interleukin-1β (IL-1β) as an inducer. In addition, the expression of the transcription factor CAAT/enhancer binding protein beta (C/EBP-β), which binds to the IL-1/IL-6 response element in the C3 promoter, was inhibited in liver biopsy specimens. Furthermore, expression of C/EBP-β was reduced in hepatocytes infected with cell culture-grown HCV, as well as in hepatocytes transfected with the NS5A genomic region of HCV. Together, these results underscore the role of HCV NS5A protein in impairing innate immune function.
Infectious Spleen and Kidney Necrosis Virus (a Fish Iridovirus) Enters Mandarin Fish Fry Cells via Caveola-Dependent Endocytosis
Authors: Guo Chang-Jun , Wu Yan-Yan , Yang Li-Shi , Yang Xiao-Bo , He Jian , Mi Shu , Jia Kun-Tong , Weng Shao-Ping , Yu Xiao-Qiang , He Jian-Guo 
Published: December 2011

ABSTRACT

Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus
Megalocytivirus
from the family
Iridoviridae
. Megalocytiviruses have been implicated in more than 50 fish species infections and currently threaten the aquaculture industry, causing great economic losses in China, Japan, and Southeast Asia. However, the cellular entry mechanisms of megalocytiviruses remain largely uncharacterized. In this study, the main internalization mechanism of ISKNV was investigated by using mandarin fish fry (MFF-1) cells. The progression of ISKNV infection is slow, and infection is not inhibited when the cells are treated with ammonium chloride (NH
4
Cl), chloroquine, sucrose, and chlorpromazine, which are inhibitors of clathrin-dependent endocytosis. The depletion of cellular cholesterol by methyl-β-cyclodextrin results in the significant inhibition of ISKNV infection; however, the infection is resumed with cholesterol replenishment. Inhibitors of caveolin-1-involved signaling events, including phorbol 12-myristate 13-acetate (PMA), genistein, and wortmannin, impair ISKNV entry into MFF-1 cells. Moreover, ISKNV entry is dependent on dynamin and the microtubule cytoskeleton. Cofraction analysis of ISKNV and caveolin-1 showed that ISKNV colocates with caveolin-1 during virus infection. These results indicate that ISKNV entry into MFF-1 cells proceeds via classical caveola-mediated endocytosis and is dependent on the microtubules that serve as tracks along which motile cavicles may move via a caveola-caveosome-endoplasmic reticulum (ER) pathway. As a fish iridovirus, ISKNV entry into MFF-1 cells is different from the clathrin-mediated endocytosis of frog virus 3 entry into mammalian cells (BHK-21) at 28°C, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection.
Subgrid Model with Scaling Laws for Atmospheric Simulations
Authors: Kitsios Vassili , Frederiksen Jorgen S. , Zidikheri Meelis J. 
Published: December 2011

AbstractSubgrid-scale parameterizations with self-similar scaling laws are developed for large-eddy simulations (LESs) of atmospheric flows. The key new contribution is the development of scaling laws that govern how these parameterizations depend on the LES resolution and flow strength. Both stochastic and deterministic representations of the effects of subgrid-scale eddies on the retained scales are considered. The stochastic subgrid model consists of a backscatter noise term and a drain eddy viscosity, while in the deterministic subgrid model the net effect of these two terms is represented by a net eddy viscosity. In both cases the subgrid transfers are calculated self-consistently from the statistics of higher-resolution-reference direct numerical simulations (DNSs). The dependence of the subgrid parameterizations on the resolution of the LESs is determined for DNSs having resolutions up to triangular 504 wavenumber truncations. The subgrid parameterizations are developed for typical large-scale atmospheric flows and for different strengths and spectra of kinetic energy within a quasigeostrophic spectral model. LESs using the stochastic and deterministic subgrid parameterizations are shown to replicate the kinetic energy spectra of the reference DNS at the scales of the LESs. It is found that the maximum strengths of the drain, net, and backscatter viscosities satisfy scaling laws dependent on the LES truncation wavenumber and that the dependence of these eddy viscosities on total wavenumber can also be written as essentially universal functions that depend on flow strength and resolution. The scaling laws make the subgrid-scale parameterizations more generally applicable in LESs and remove the need to generate them from reference DNSs.
Possible Impacts of Climate Change on Wind Gusts under Downscaled Future Climate Conditions over Ontario, Canada
Authors: Cheng Chad Shouquan , Li Guilong , Li Qian , Auld Heather , Fu Chao 
Published: December 2011

Hourly/daily wind gust simulation models and regression-based downscaling methods were developed to assess possible impacts of climate change on future hourly/daily wind gust events over the province of Ontario, Canada. Since the climate/weather validation process is critical, a formal model result verification process has been built into the analysis to ascertain whether the methods are suitable for future projections. The percentage of excellent and good simulations among all studied seven wind gust categories ranges from 94% to 100% and from 69% to 95%, respectively, for hourly and daily wind gusts, for both model development and validation. The modeled results indicate that frequencies of future hourly/daily wind gust events are projected to increase late this century over the study area under a changing climate. For example, across the study area, the annual mean frequency of future hourly wind gust events ≥28, ≥40, and ≥70 km h−1 for the period 2081–2100 derived from the ensemble of downscaled eight-GCM A2 simulations is projected to be about 10%–15%, 10%–20%, and 20%–40% greater than the observed average during the period 1994–2007, respectively. The corresponding percentage increase for future daily wind gust events is projected to be <10%, ~10%, and 15%–25%. Inter-GCM-model and interscenario uncertainties of future wind gust projections were quantitatively assessed. On average, projected percentage increases in frequencies of future hourly/daily wind gust events ≥28 and ≥40 km h−1 are about 90%–100% and 60%–80% greater than inter-GCM-model–interscenario uncertainties, respectively. For wind gust events ≥70 km h−1, the corresponding projected percentage increases are about 25%–35% greater than the interscenario uncertainties and are generally similar to inter-GCM-model uncertainties.
Efficacy of low level laser therapy associated with exercises in knee osteoarthritis: a randomized double-blind study
Authors: Alfredo Patrícia Pereira , Bjordal Jan Magnus , Dreyer Sílvia Helena , Meneses Sarah Rúbia Ferreira , Zaguetti Giovana , Ovanessian Vanessa , Fukuda Thiago Yukio , Junior Washington Steagall , Martins Rodrigo Álvaro Brandão Lopes , Casarotto Raquel Aparecida , Marques Amélia Pasqual 
Published: December 2011

Objectives: To estimate the effects of low level laser therapy in combination with a programme of exercises on pain, functionality, range of motion, muscular strength and quality of life in patients with osteoarthritis of the knee. Design: A randomized double-blind placebo-controlled trial with sequential allocation of patients to different treatment groups. Setting: Special Rehabilitation Services. Subjects: Forty participants with knee osteoarthritis, 2–4 osteoarthritis degree, aged between 50 and 75 years and both genders. Intervention: Participants were randomized into one of two groups: the laser group (low level laser therapy dose of 3 J and exercises) or placebo group (placebo laser and exercises). Main measures: Pain was assessed using a visual analogue scale (VAS), functionality using the Lequesne questionnaire, range of motion with a universal goniometer, muscular strength using a dynamometer, and activity using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire at three time points: (T1) baseline, (T2) after the end of laser therapy (three weeks) and (T3) the end of the exercises (11 weeks). Results: When comparing groups, significant differences in the activity were also found ( P = 0.03). No other significant differences ( P > 0.05) were observed in other variables. In intragroup analysis, participants in the laser group had significant improvement, relative to baseline, on pain ( P = 0.001), range of motion ( P = 0.01), functionality ( P = 0.001) and activity ( P < 0.001). No significant improvement was seen in the placebo group. Conclusion: Our findings suggest that low level laser therapy when associated with exercises is effective in yielding pain relief, function and activity on patients with osteoarthritis of the knees.
Activities-specific Balance Confidence (ABC) Scale adapted for the mainland population of China
Authors: Guan Qiang , Han Hongjie , Li Yunxia , Zhao Lijuan , Jin Lingjing , Zhan Qing 
Published: December 2011

Objective: To evaluate the reliability and validity of a Chinese Mandarin version of the Activities-specific Balance Confidence (ABC) Scale. Design: Cross-sectional. Setting: A rehabilitation centre for adults. Participants: Sixty-one elderly people living in the community. Main outcome measure: Self-efficacy in balancing ability was assessed via a Mandarin Chinese version of the ABC Scale. Results: The intraclass correlation coefficients for test–retest and inter-rater reliability of the Chinese Mandarin version of the ABC Scale were 0.98 (95% confidence interval (CI) 0.96–0.99) and 0.96 (95% CI 0.94–0.98), respectively. The Cronbach’s α coefficient of internal consistency was 0.94. In the Bland–Altman analysis the mean difference in the ABC test–retest scores was −1.81, and the 95% limits of agreement varied from −10.67 to 7.03. The evaluation of inter-rater reliability showed that the mean difference was −1.13, and the 95% limits of agreement varied from −9.55 to 7.30. The factor analysis method was adopted to assess the validity of the scaled activities and two factors contributed to total variance at 52.5% and 13.6%, respectively. Conclusion: The Chinese Mandarin version of the ABC Scale is reliable and valid, and is suitable for assessments of balance confidence in aged people in mainland China.
Reproducibility, validity and responsiveness of the 200-metre fast walk test in patients undergoing cardiac rehabilitation
Authors: Gremeaux V , Hannequin A , Laroche D , Deley G , Duclay J , Casillas JM 
Published: December 2011

Objective: To investigate the reliability, validity and responsiveness of the 200-metre fast walk test in patients with coronary artery disease engaged in a cardiac rehabilitation programme. Design: Descriptive study. Setting: Tertiary care hospital. Subjects: Thirty stable patients with coronary artery disease (51.9 ± 8.7 years), referred to the cardiac rehabilitation department after an acute coronary syndrome. Intervention: Not applicable. Main measures: Six-minute walk test distance, time to perform the 200-m fast walk test, peak power output of the graded maximal exercise test, before and after the programme; SF-36 quality of life questionnaire at baseline. Walk tests were performed twice at baseline to assess reliability. Results: The 200-m fast walk test was highly reliable (ICC = 0.97). It was significantly correlated with the graded maximal exercise test peak power and the 6-minute walk test at baseline ( r = −0.417; P < 0.05; and r = −0.566; P < 0.01, respectively) and after the training programme ( r = −0.460, P < 0.05; and r = −0.926; P < 0.01, respectively). At baseline, there was a strong correlation between the 200-m fast walk test time and the physical component score of the SF-36 ( r = −0.77; P < 0.01), but not between the 200-m fast walk test time and the SF-36 mental component score. Mean 200-m fast walk test time was significantly different between the patients performing ≤90 W ( n = 11) or ≥100 W ( n = 19) at the baseline graded maximal exercise test (121.7 ± 13.6 vs. 115.5 ± 10.1 seconds; P < 0.05). The responsiveness was strong with a standardized response mean at 1.11. Conclusion: The 200-m fast walk test is a reliable, valid and responsive high-intensity walk test in patients with coronary artery disease after an acute coronary syndrome. It can thus give additional information to that given by the 6-minute walk test and the graded maximal exercise test.
Challenges faced by older adults with vision loss: a qualitative study with implications for rehabilitation
Authors: Cimarolli Verena R , Boerner Kathrin , Brennan-Ing Mark , Reinhardt Joann P , Horowitz Amy 
Published: December 2011

Objective: To provide an in-depth assessment of challenges faced by older adults with recent vision loss and to determine changes in the nature of these challenges over time for the purpose of informing the design of vision rehabilitation services. Design: Longitudinal, qualitative study with three time points. Setting: Vision rehabilitation agency. Subjects: Three hundred and sixty-four older adults aged 65 with significant vision impairment due to age-related macular degeneration. Interventions: In-person interviews conducted at baseline, one year and two years and coded using a qualitative analytical approach. Main measures: Open-ended questions assessing challenges faced due to vision loss in functional, social and psychological life domains. Results: Almost all participants reported a wide variety of challenges across all three domains with the most variety in the functional domain. Over a two-year period, functional challenges (e.g. using transportation) increased, social challenges (e.g. recognizing people) remained stable, and psychological challenges (e.g. negative affect) decreased overall. Conclusions: Although functional challenges are predominant, social and psychological challenges are quite common and need to be addressed in vision rehabilitation. Rehabilitation planning should also consider that vision-related challenges can change over time.