bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Cytomegalovirus IE1-72 Protein Interacts with p53 and Inhibits p53-Dependent Transactivation by a Mechanism Different from That of IE2-86 Protein
Authors: Hwang Eung-Soo , Zhang Zhigang , Cai Haobin , Huang David Y. , Huong Shu-Mei , Cha Chang-Yong , Huang Eng-Shang 
Published: September 2009

ABSTRACT
Infection of host cells with human cytomegalovirus (HCMV) induces cell cycle dysregulation. Two HCMV immediate-early (IE) proteins, IE1-72 and IE2-86, are promiscuous transactivators that have been implicated in the dysregulatory events. Cellular p53 protein is accumulated to high levels in HCMV-infected cells, but the indicative marker of p53 transcriptional activity, p21, is markedly decreased. Both IE1-72 and IE2-86 were able to transactivate the p53 promoter and interact with p53 protein in DNA-transfected or HCMV-infected cells. HCMV UL84, a multiregulatory protein expressed in early periods of HCMV infection, also interacted with p53. HCMV IE1-72 prevented or disrupted p53 binding to p53-specific DNA sequences, while IE2-86 and/or UL84 enhanced p53 binding and induced supershift of this DNA-protein complex. Both HCMV IE1-72 and IE2-86 were able to inhibit p53-dependent transcriptional activation in plasmid-transfected cells. IE1-72, rather than IE2-86, was found to be responsible for p21 downregulation in HCMV-infected HEL cells. DNA transfection analysis using IE1-72 mutants revealed that exon 2/3 and the zinc finger region of IE1-72 are essential for IE1-72's effect on the repression of p53-dependent transcriptional activation. These data suggest that HCMV IE1-72 and/or IE2-86 transactivates the p53 promoter and induces p53 accumulation, but HCMV IE1-72 represses the p53 transactivation activity by a unique binding hindrance mechanism different from that of IE2-86. Thus, various modes of viral IE proteins and p53 interactions might result in multiple outcomes, such as stimulation of cellular DNA synthesis, cell cycle progression and cell cycle arrest, and prevention of program cell death.
Protective Efficacy and Immunogenicity of an Adenoviral Vector Vaccine Encoding the Codon-Optimized F Protein of Respiratory Syncytial Virus
Authors: Kohlmann Rebekka , Schwannecke Sarah , Tippler Bettina , Ternette Nicola , Temchura Vladimir V. , Tenbusch Matthias , Überla Klaus , Grunwald Thomas 
Published: September 2009

ABSTRACTAdenoviral vectors (AdV) have received considerable attention for vaccine development because of their high immunogenicity and efficacy. In previous studies, it was shown that DNA immunization of mice with codon-optimized expression plasmids encoding the fusion protein of respiratory syncytial virus (RSV F) resulted in enhanced protection against RSV challenge compared to immunization with plasmids carrying the wild-type cDNA sequence of RSV F. In this study, we constructed AdV carrying the codon-optimized full-length RSV F gene (AdV-F) or the soluble form of the RSV F gene (AdV-Fsol). BALB/c mice were immunized twice with AdV-F or AdV-Fsol and challenged with RSV intranasally. Substantial levels of antibody to RSV F were induced by both AdV vaccines, with peak neutralizing-antibody titers of 1:900. Consistently, the viral loads in lung homogenates and bronchoalveolar lavage fluids were significantly reduced by a factor of more than 60,000. The protection against viral challenge could be measured even 8 months after the booster immunization. AdV-F and AdV-Fsol induced similar levels of immunogenicity and protective efficacy. Therefore, these results encourage further development of AdV vaccines against RSV infection in humans.
Molecular Chaperone BiP Interacts with Borna Disease Virus Glycoprotein at the Cell Surface
Authors: Honda Tomoyuki , Horie Masayuki , Daito Takuji , Ikuta Kazuyoshi , Tomonaga Keizo 
Published: September 2009

ABSTRACTBorna disease virus (BDV) is characterized by highly neurotropic infection. BDV enters its target cells using virus surface glycoprotein (G), but the cellular molecules mediating this process remain to be elucidated. We demonstrate here that the N-terminal product of G, GP1, interacts with the 78-kDa chaperone protein BiP. BiP was found at the surface of BDV-permissive cells, and anti-BiP antibody reduced BDV infection as well as GP1 binding to the cell surface. We also reveal that BiP localizes at the synapse of neurons. These results indicate that BiP may participate in the cell surface association of BDV.
Packaging of Host mY RNAs by Murine Leukemia Virus May Occur Early in Y RNA Biogenesis
Authors: Garcia Eric L. , Onafuwa-Nuga Adewunmi , Sim Soyeong , King Steven R. , Wolin Sandra L. , Telesnitsky Alice 
Published: September 2009

ABSTRACT
Moloney murine leukemia virus (MLV) selectively encapsidates host mY1 and mY3 RNAs. These noncoding RNA polymerase III transcripts are normally complexed with the Ro60 and La proteins, which are autoantigens associated with rheumatic disease that function in RNA biogenesis and quality control. Here, MLV replication and mY RNA packaging were analyzed using Ro60 knockout embryonic fibroblasts, which contain only ∼3% as much mY RNA as wild-type cells. Virus spread at the same rate in wild-type and Ro knockout cells. Surprisingly, MLV virions shed by Ro60 knockout cells continued to package high levels of mY1 and mY3 (about two copies of each) like those from wild-type cells, even though mY RNAs were barely detectable within producer cells. As a result, for MLV produced in Ro60 knockout cells, encapsidation selectivity from among all cell RNAs was even higher for mY RNAs than for the viral genome. Whereas mY RNAs are largely cytoplasmic in wild-type cells, fractionation of knockout cells revealed that the residual mY RNAs were relatively abundant in nuclei, likely reflecting the fact that most mY RNAs were degraded shortly after transcription in the absence of Ro60. Together, these data suggest that these small, labile host RNAs may be recruited at a very early stage of their biogenesis and may indicate an intersection of retroviral assembly and RNA quality control pathways.
Epstein-Barr Virus Nuclear Protein 3C Domains Necessary for Lymphoblastoid Cell Growth: Interaction with RBP-Jκ Regulates TCL1
Authors: Lee Sungwook , Sakakibara Shuhei , Maruo Seiji , Zhao Bo , Calderwood Michael A. , Holthaus Amy M. , Lai Chiou-Yan , Takada Kenzo , Kieff Elliott , Johannsen Eric 
Published: September 2009

ABSTRACT

B lymphocytes converted into lymphoblastoid cell lines (LCLs) by an Epstein-Barr virus that expresses a conditional EBNA3C require complementation with EBNA3C for growth under nonpermissive conditions. Complementation with relatively large EBNA3C deletion mutants identified amino acids (aa) 1 to 506 (which includes the RBP-Jκ/CSL [RBP-Jκ] binding domain) and 733 to 909 to be essential for LCL growth, aa 728 to 732 and 910 to 992 to be important for full wild-type (wt) growth, and only aa 507 to 727 to be unimportant (S. Maruo, Y. Wu, T. Ito, T. Kanda, E. D. Kieff, and K. Takada, Proc. Natl. Acad. Sci. USA
106:
4419-4424, 2009). When mutants with smaller deletions were used, only aa 51 to 400 and 851 to 900 were essential for LCL growth; aa 447 to 544, 701 to 750, 801 to 850, and 901 to 992 were important for full wt growth; and aa 4 to 50, 401 to 450, 550 to 707, and 751 to 800 were unimportant. These data reduce the EBNA3C essential residues from 68% to 40% of the open reading frame. Point mutations confirmed RBP-Jκ binding to be essential for wt growth and indicated that SUMO and CtBP binding interactions were important only for full wt growth. EBNA3C aa 51 to 150, 249 to 311, and 851 to 900 were necessary for maintaining LCL growth, but not RBP-Jκ interaction, and likely mediate interactions with other key cell proteins. Moreover, all mutants null for LCL growth had fewer S+G
2
/M-phase cells at 14 days, consistent with EBNA3C interaction with RBP-Jκ as well as aa 51 to 150, 249 to 311, and 851 to 900 being required to suppress p16
INK4A
(S. Maruo, Y. Wu, S. Ishikawa, T. Kanda, D. Iwakiri, and K. Takada, Proc. Natl. Acad. Sci. USA
103:
19500-19505, 2006). We have confirmed that EBNA3C upregulates TCL1 and discovered that EBNA3C upregulates TCL1 through RBP-Jκ, indicating a central role for EBNA3C interaction with RBP-Jκ in mediating cell gene transcription.
Hepatoma Cell Density Promotes Claudin-1 and Scavenger Receptor BI Expression and Hepatitis C Virus Internalization
Authors: Schwarz Anne K. , Grove Joe , Hu Ke , Mee Christopher J. , Balfe Peter , McKeating Jane A. 
Published: September 2009

ABSTRACTHepatitis C virus (HCV) entry occurs via a pH- and clathrin-dependent endocytic pathway and requires a number of cellular factors, including CD81, the tight-junction proteins claudin 1 (CLDN1) and occludin, and scavenger receptor class B member I (SR-BI). HCV tropism is restricted to the liver, where hepatocytes are tightly packed. Here, we demonstrate that SR-BI and CLDN1 expression is modulated in confluent human hepatoma cells, with both receptors being enriched at cell-cell junctions. Cellular contact increased HCV pseudoparticle (HCVpp) and HCV particle (HCVcc) infection and accelerated the internalization of cell-bound HCVcc, suggesting that the cell contact modulation of receptor levels may facilitate the assembly of receptor complexes required for virus internalization. CLDN1 overexpression in subconfluent cells was unable to recapitulate this effect, whereas increased SR-BI expression enhanced HCVpp entry and HCVcc internalization, demonstrating a rate-limiting role for SR-BI in HCV internalization.
Jaagsiekte Sheep Retrovirus Encodes a Regulatory Factor, Rej, Required for Synthesis of Gag Protein
Authors: Hofacre Andrew , Nitta Takayuki , Fan Hung 
Published: September 2009

ABSTRACT

Retroviruses express Gag and Pol proteins by translation of unspliced genome-length viral RNA. For some retroviruses, transport of unspliced viral RNA to the cytoplasm is mediated by small regulatory proteins such as human immunodeficiency virus Rev, while other retroviruses contain constitutive transport elements in their RNAs that allow transport without splicing. In this study, we found that the betaretrovirus Jaagsiekte sheep retrovirus (JSRV) encodes within the
env
gene a
trans
-acting factor (Rej) necessary for the synthesis of Gag protein from unspliced viral RNA. Deletion of
env
sequences from a JSRV proviral expression plasmid (pTN3) abolished its ability to produce Gag polyprotein in transfected 293T cells, and Gag synthesis could be restored by cotransfection of an
env
expression plasmid (ΔGP). Deletion analysis localized the complementing activity (Rej) to the putative Env signal peptide, and a signal peptide expression construct showed Rej activity. Two other betaretroviruses, mouse mammary tumor virus (MMTV) and human endogenous retrovirus type K, encode analogous factors (Rem and Rec, respectively) that are encoded from doubly spliced
env
mRNAs. Reverse transcriptase-PCR cloning and sequencing identified alternate internal splicing events in the 5′ end of JSRV
env
that could signify analogous doubly spliced Rej mRNAs, and cDNA clones expressing two of them also showed Rej activity. The predicted Rej proteins contain motifs similar to those found in MMTV Rem and other analogous retroviral regulatory proteins. Interestingly, in most cell lines, JSRV expression plasmids with Rej deleted showed normal transport of unspliced JSRV RNA to the cytoplasm; however, in 293T cells Rej modestly enhanced export of unspliced viral RNA (2.8-fold). Metabolic labeling experiments with [
35
S]methionine indicated that JSRV Rej is required for the synthesis of viral Gag polyprotein. Thus, in most cell lines, the predominant function of Rej is to facilitate translation of unspliced viral mRNA.
Programmed health surveillance and detection of emerging diseases in occupational health: contribution of the French national occupational disease surveillance and prevention network (RNV3P)
Authors: Bonneterre Vincent , Faisandier Laurie , Bicout Dominique , Bernardet Cyril , Piollat Jacques , Ameille Jacques , de Clavière Caroline , Aptel Michel , Lasfargues Gérard , de Gaudemaris Régis ,   for RNV3P
Published: September 2009

ObjectiveThe French national occupational disease surveillance and prevention network (RNV3P) includes the 30 occupational disease consultation centres in university hospitals to which patients are referred for potentially work-related diseases, and an occupational health service. The aim of this work is to demonstrate the contribution of RNV3P to national health surveillance.MethodsData from consultations are recorded in standardised occupational health reports and coded using international or national classifications. Programmed health surveillance is carried out through annual follow-up of annual referrals to experts for pre-selected disease–exposure associations, as well as incidence estimations for the well characterised working population followed by the occupational health service. Hypotheses on new emerging diseases are generated using statistical methods employed in pharmacosurveillance and by modelling as an exposome to analyse multiple exposures.Results58 777 occupational health reports were collected and analysed from 2001 to 2007. Referrals to the 30 university hospital centres increased significantly for asbestos-related diseases, mood disorders and adjustment disorders related to psychological and organisational demands, and for elbow and shoulder disorders related to manual handling. Referrals significantly decreased for asthma and for rhinitis related to exposure to organic dusts (vegetable or animal) or chemicals, except for cosmetics and cleaning products. Estimation of incidences by the occupational health services showed different patterns in different sectors of activity. The methods for detecting emerging diseases are presented and illustrated using the example of systemic sclerosis, identifying new exposures and new sectors of activity to be investigated.ConclusionThe RNV3P collects data from two complementary samples: 30 university hospital centres (workers or former workers) and an occupational health service (current workers). This dual approach is useful for surveillance and for hypothesis generation on new emerging disease–exposure associations.
The Delayed Effect of Major El Niño Events on Indian Monsoon Rainfall
Authors: Park Hyo-Seok , Chiang John C. H. , Lintner Benjamin R. , Zhang Guang J. 
Published: September 2009

Abstract
Previous studies have shown that boreal summer Indian monsoon rainfall is, on average, significantly above normal after major El Niño events. In this study, the underlying causes of this rainfall response are examined using both observational analysis and atmospheric general circulation model (AGCM) simulations. Moist static energy budgets for two strong El Niño events (1982/83 and 1997/98), estimated from monthly 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40), suggest that stronger low-level moisture transport and reduced moist stability associated with a warmer north Indian Ocean (NIO) can increase monsoon rainfall, despite a weakened monsoon circulation.
The trade-off between a dynamically weaker monsoon and moist processes favoring enhanced monsoonal rainfall is broken during the late monsoon season (August–September) as the warm NIO enhances surface latent heat flux and the monsoon circulation relaxes back to the climatological mean. The monsoon circulation strength and the moist processes work together in the late season, which explains the observed tendency for monsoonal rainfall increases during the late monsoon season after strong winter El Niño conditions.
Idealized AGCM experiments with a fixed-depth ocean mixed layer demonstrate that the remnant but weaker-than-peak warm SSTs in the eastern equatorial Pacific during spring and the early summer following winter El Niños substantially contribute to the NIO warming. The results suggest that local air–sea interactions in the tropical Indian Ocean after winter El Niño are strongly dependent on the details of El Niño’s decaying trend.
The Influence of the Madden–Julian Oscillation on Tropical Cyclone Activity in the Fiji Region
Authors: Chand Savin S. , Walsh Kevin J. E. 
Published: September 2009

AbstractThis study examines the modulation of tropical cyclone (TC) activity by the Madden–Julian oscillation (MJO) in the Fiji, Samoa, and Tonga regions (FST region), using Joint Typhoon Warning Center best-track cyclone data and the MJO index developed by Wheeler and Hendon. Results suggest strong MJO–TC relationships in the FST region. The TC genesis patterns are significantly altered over the FST region with approximately 5 times more cyclones forming in the active phase than in the inactive phase of the MJO. This modulation is further strengthened during El Niño periods. The large-scale environmental conditions (i.e., low-level relative vorticity, upper-level divergence, and vertical wind shear) associated with TC genesis show a distinct patterns of variability for the active and inactive MJO phases. The MJO also has a significant effect on hurricane category and combined gale and storm category cyclones in the FST region. The occurrences of both these cyclone categories are increased in the active phase of the MJO, which is associated with enhanced convective activity. The TCs in the other MJO phases where convective activity is relatively low, however, show a consistent pattern of increase in hurricane category cyclones and a concomitant decrease in gale and storm category cyclones. Finally, TC tracks in different MJO phases are also objectively described using a cluster analysis technique. Patterns seen in the clustered track regimes are well explained here in terms of 700–500-hPa mean steering flow.
Dance and Peer Support to Improve Diabetes Outcomes in African American Women
Authors: Murrock Carolyn J. , Higgins Patricia A. , Killion Cheryl 
Published: September 2009

Purpose The purpose of this pilot study was to test a dance intervention and explore the role of peer support to improve the diabetes outcomes of A1C, weight, body fat, and blood pressure in African American women with type 2 diabetes. Methods This study was conducted in a community-based outpatient clinic. A mixed methods design was used. A total of 46 women, 26 to 83 years of age, were randomized to either the 12-week dance group or usual care group. Both between group and intraindividual group differences were analyzed from baseline to 12 weeks. Focus group interviews explored the role of peer support through semistructured discussions for the women enrolled in the dance group. Results Results showed significant group mean differences in systolic blood pressure (BP) and body fat. Paired t tests showed significant reductions in all the diabetes outcomes for the dance group and significant increases in glycolated hemoglobin (A1C) and systolic BP for the usual care group. The emergent themes of the focus groups were that a diabetes diagnosis was devastating, and changing eating habits and taking medications was often difficult. Peer support in the dance group was expressed as camaraderie, enjoyment, and laughter, which fostered attendance. Conclusions Dancing 2 times per week for 12 weeks produced significant group differences in systolic BP and body fat and significant intraindividual changes. The implications are that dancing in a supportive environment with peers may be an effective strategy for diabetes educators to help those with diabetes to become more physically active and improve diabetes outcomes and overall health.
Development and initial validation of the Northwick Park Therapy Dependency Assessment
Authors: Turner-Stokes Lynne , Shaw Asa , Law Janet , Rose Hilary 
Published: September 2009

Objectives: To describe the development and initial validation of the Northwick Park Therapy Dependency Assessment (NPTDA) as a measure of therapy interventions in neurorehabilitation. Design: An iterative development process, followed by comparison with systemic prospective activity analysis, and parallel application of prospective and retrospective scores Setting: A tertiary specialist inpatient neurorehabilitation service Participants: A total of 37 patients (M:F 21:16, mean age 41.8 (SD 14.7) years) with complex neurological disability in two consecutive cross-sectional cohorts. Methods: The NPTDA was developed and refined over 18 months, together with an algorithm that converts ordinal scores to estimated therapy hours/week. NPTDA-estimated hours were compared with ‘actual’ therapy hours/week, identified from activity analysis. In a subsequent cohort analysis, prospectively rated NPTDA scores (reflecting intended levels of intervention) were compared with retrospective NPTDA scores (actual interventions). Results: NPTDA-estimated therapy hours/week were strongly correlated with those identified from activity analysis, for total scores (Spearman rho 0.77, P<0.0001), and also for all five subdomains for direct (hands-on) intervention (rho 0.70—0.93, P<0.0001). The initial test algorithm overestimated therapy hours (Wilcoxon z =3.9, P<0.001). After adjustment, reanalysis using a revised algorithm showed this bias to be removed (Wilcoxon z =1.4 P =0.15). Prospective and retrospectively applied total NPTDA scores were strongly correlated (rho 0.61, P<0.0001). Although intended levels of intervention were higher than those actually delivered (Wilcoxon z =3.30, P<0.001), the differences corresponded to real deviations from intended practice. Conclusion: In this initial evaluation, after revision of the algorithm, the NPTDA provided acceptable estimate of therapy interventions. Further evaluation is now required in other populations and settings.
Revision Open Bankart Surgery After Arthroscopic Repair for Traumatic Anterior Shoulder Instability
Authors: Cho Nam Su , Yi Jin Woong , Lee Bong Gun , Rhee Yong Girl 
Published: September 2009

Background Only a few studies have provided homogeneous analysis of open revision surgery after a failed arthroscopic Bankart procedure. Hypothesis Open Bankart revision surgery will be effective in a failed arthroscopic anterior stabilization but inevitably results in a loss of range of motion, especially external rotation. Study Design Case series; Level of evidence, 4. Methods Twenty-six shoulders that went through traditional open Bankart repair as revision surgery after a failed arthroscopic Bankart procedure for traumatic anterior shoulder instability were enrolled for this study. The mean patient age at the time of revision surgery was 24 years (range, 16–38 years), and the mean duration of follow-up was 42 months (range, 25–97 months). Results The preoperative mean range of motion was 173° in forward flexion and 65° in external rotation at the side. After revision surgery, the ranges measured 164° and 55°, respectively ( P = .024 and .012, respectively). At the last follow-up, the mean Rowe score was 81 points, with 88.5% of the patients reporting good or excellent results. After revision surgery, redislocation developed in 3 shoulders (11.5%), all of which had an engaging Hill-Sachs lesion and associated hyperlaxity (2+ or greater laxity on the sulcus sign). Conclusion Open revision Bankart surgery for a failed arthroscopic Bankart repair can provide a satisfactory outcome, including a low recurrence rate and reliable functional return. In open revision Bankart surgery after failed stabilization for traumatic anterior shoulder instability, the surgeon should keep in mind the possibility of a postoperative loss of range of motion and a thorough examination for not only a Bankart lesion but also other associated lesions, including a bone defect or hyperlaxity, to lower the risk of redislocation.