bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adaptation of Saffold Virus 2 for High-Titer Growth in Mammalian Cells
Authors: Hertzler Shannon , Liang Zhiguo , Treso Balint , Lipton Howard L. 
Published: May 2011

ABSTRACT

Saffold viruses (SAFV) are a recently discovered group of human
Cardioviruses
closely related to Theiler's murine encephalomyelitis viruses (TMEV). Unlike TMEV and encephalomyocarditis virus, each of which is monotypic, SAFV are genetically diverse and include at least eight genotypes. To date, only Saffold virus 3 (SAFV-3) has been grown efficiently in mammalian cells
in vitro
. Here, we report the successful adaptation of SAFV-2 for efficient growth in HeLa cells after 13 passages in the alpha/beta interferon-deficient human glial cell line U118 MG. Nine amino acid changes were found in the adapted virus, with single mutations in VP2, VP3, and 2B, while 6 mutations arose in VP1. Most capsid mutations were in surface loops. Analysis of SAFV-2 revealed virus growth and cytopathic effect only in human cell lines, with large plaques forming in HeLa cells, with minimal cell association, and without using sialic acid to enter cells. Despite the limited growth of SAFV-2 in rodent cells
in vitro
, BALB/c mice inoculated with SAFV-2 showed antibody titers of >1:10
6
, and fluorescence-activated cell sorting (FACS) analysis revealed only minimal cross-reactivity with SFV-3. Intracerebral inoculation of 6-week-old FVB/n mice produced paralysis and acute neuropathological changes, including meningeal infiltrates, encephalitis, particularly of the limbic system, and spinal cord white matter inflammation.
NS4B Self-Interaction through Conserved C-Terminal Elements Is Required for the Establishment of Functional Hepatitis C Virus Replication Complexes
Authors: Paul David , Romero-Brey Inés , Gouttenoire Jérôme , Stoitsova Savina , Krijnse-Locker Jacomine , Moradpour Darius , Bartenschlager Ralf 
Published: May 2011

ABSTRACT
Hepatitis C virus (HCV) is an important human pathogen, persistently infecting more than 170 million individuals worldwide. Studies of the HCV life cycle have become possible with the development of cell culture systems supporting the replication of viral RNA and the production of infectious virus. However, the exact functions of individual proteins, especially of nonstructural protein 4B (NS4B), remain poorly understood. NS4B triggers the formation of specific, vesicular membrane rearrangements, referred to as membranous webs, which have been reported to represent sites of HCV RNA replication. However, the mechanism of vesicle induction is not known. In this study, a panel of 15 mutants carrying substitutions in the highly conserved NS4B C-terminal domain was generated. Five mutations had only a minor effect on replication, but two of them enhanced assembly and release of infectious virus. Ten mutants were replication defective and used for selection of pseudoreversions. Most of the pseudoreversions also localized to the highly conserved NS4B C-terminal domain and were found to restore replication competence upon insertion into the corresponding primary mutant. Importantly, pseudoreversions restoring replication competence also restored heterotypic NS4B self-interaction, which was disrupted by the primary mutation. Finally, electron microscopy analyses of membrane alterations induced by NS4B mutants revealed striking morphological abnormalities, which were restored to wild-type morphology by the corresponding pseudoreversion. These findings demonstrate the important role of the C-terminal domain in NS4B self-interaction and the formation of functional HCV replication complexes.
Neutralizing Monoclonal Antibodies against Hepatitis C Virus E2 Protein Bind Discontinuous Epitopes and Inhibit Infection at a Postattachment Step
Authors: Sabo Michelle C. , Luca Vincent C. , Prentoe Jannick , Hopcraft Sharon E. , Blight Keril J. , Yi MinKyung , Lemon Stanley M. , Ball Jonathan K. , Bukh Jens , Evans Matthew J. , Fremont Daved H. , Diamond Michael S. 
Published: May 2011

ABSTRACT
The E2 glycoprotein of hepatitis C virus (HCV) mediates viral attachment and entry into target hepatocytes and elicits neutralizing antibodies in infected patients. To characterize the structural and functional basis of HCV neutralization, we generated a novel panel of 78 monoclonal antibodies (MAbs) against E2 proteins from genotype 1a and 2a HCV strains. Using high-throughput focus-forming reduction or luciferase-based neutralization assays with chimeric infectious HCV containing structural proteins from both genotypes, we defined eight MAbs that significantly inhibited infection of the homologous HCV strain in cell culture. Two of these bound E2 proteins from strains representative of HCV genotypes 1 to 6, and one of these MAbs, H77.39, neutralized infection of strains from five of these genotypes. The three most potent neutralizing MAbs in our panel, H77.16, H77.39, and J6.36, inhibited infection at an early postattachment step. Receptor binding studies demonstrated that H77.39 inhibited binding of soluble E2 protein to both CD81 and SR-B1, J6.36 blocked attachment to SR-B1 and modestly reduced binding to CD81, and H77.16 blocked attachment to SR-B1 only. Using yeast surface display, we localized epitopes for the neutralizing MAbs on the E2 protein. Two of the strongly inhibitory MAbs, H77.16 and J6.36, showed markedly reduced binding when amino acids within hypervariable region 1 (HVR1) and at sites ∼100 to 200 residues away were changed, suggesting binding to a discontinuous epitope. Collectively, these studies help to define the structural and functional complexity of antibodies against HCV E2 protein with neutralizing potential.
Arginine Methylation of the RGG Box Does Not Appear To Regulate ICP27 Import during Herpes Simplex Virus Infection
Authors: Souki Stuart K. , Hernandez Felicia P. , Sandri-Goldin Rozanne M. 
Published: May 2011

ABSTRACT

Arginine methylation can regulate protein import and export and can modulate protein interactions. Herpes simplex virus 1 (HSV-1) ICP27 is a shuttling protein involved in viral mRNA export. We previously reported that ICP27 is methylated on three arginines within its RGG box and that arginine methylation regulates ICP27 export and its interaction with SRPK1 and Aly/REF. Here, we report that ICP27 was efficiently imported into the nucleus when hypomethylated as determined by
F
luorescence
R
ecovery
A
fter
P
hotobleaching (FRAP). Furthermore, coimmunoprecipitation of ICP27 with β-importin was not significantly affected by ICP27 hypomethylation. Thus, ICP27 import does not appear to be regulated by arginine methylation.
Viral Replication and Innate Host Responses in Primary Human Alveolar Epithelial Cells and Alveolar Macrophages Infected with Influenza H5N1 and H1N1 Viruses
Authors: Yu Wendy C. L. , Chan Renee W. Y. , Wang Jieru , Travanty Emily A. , Nicholls John M. , Peiris J. S. Malik , Mason Robert J. , Chan Michael C. W. 
Published: May 2011

ABSTRACT
Highly pathogenic influenza H5N1 virus continues to pose a threat to public health. Although the mechanisms underlying the pathogenesis of the H5N1 virus have not been fully defined, it has been suggested that cytokine dysregulation plays an important role. As the human respiratory epithelium is the primary target cell for influenza viruses, elucidating the viral tropism and innate immune responses of influenza H5N1 virus in the alveolar epithelium may help us to understand the pathogenesis of the severe pneumonia associated with H5N1 disease. Here we used primary cultures of differentiated human alveolar type II cells, alveolar type I-like cells, and alveolar macrophages isolated from the same individual to investigate viral replication competence and host innate immune responses to influenza H5N1 (A/HK/483/97) and H1N1 (A/HK/54/98) virus infection. The viral replication kinetics and cytokine and chemokine responses were compared by quantitative PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA). We demonstrated that influenza H1N1 and H5N1 viruses replicated productively in type II cells and type I-like cells although with different kinetics. The H5N1 virus replicated productively in alveolar macrophages, whereas the H1N1 virus led to an abortive infection. The H5N1 virus was a more potent inducer of proinflammatory cytokines and chemokines than the H1N1 virus in all cell types. However, higher levels of cytokine expression were observed for peripheral blood monocyte-derived macrophages than for alveolar macrophages in response to H5N1 virus infection. Our findings provide important insights into the viral tropisms and host responses of different cell types found in the lung and are relevant to an understanding of the pathogenesis of severe human influenza disease.
NSs Protein of Rift Valley Fever Virus Promotes Posttranslational Downregulation of the TFIIH Subunit p62
Authors: Kalveram Birte , Lihoradova Olga , Ikegami Tetsuro 
Published: May 2011

ABSTRACT

Rift Valley fever virus (RVFV; family
Bunyaviridae
, genus
Phlebovirus
) is an important emerging pathogen of humans and ruminants. Its NSs protein has previously been identified as a major virulence factor that suppresses host defense through three distinct mechanisms: it directly inhibits beta interferon (IFN-β) promoter activity, it promotes the degradation of double-stranded RNA-dependent protein kinase (PKR), and it suppresses host transcription by disrupting the assembly of the basal transcription factor TFIIH through sequestration of its p44 subunit. Here, we report that in addition to PKR, NSs also promotes the degradation of the TFIIH subunit p62. Infection of cells with the RVFV MP-12 vaccine strain reduced p62 protein levels to below the detection limit early in the course of infection. This NSs-mediated downregulation of p62 was posttranslational, as it was unaffected by pharmacological inhibition of transcription or translation and MP-12 infection had no effect on p62 mRNA levels. Treatment of cells with proteasome inhibitors but not inhibition of lysosomal acidification or nuclear export resulted in a stabilization of p62 in the presence of NSs. Furthermore, p62 could be coprecipitated with NSs from lysates of infected cells. These data suggest that the RVFV NSs protein is able to interact with the TFIIH subunit p62 inside infected cells and promotes its degradation, which can occur directly in the nucleus.
Hepatitis C Virus Hijacks P-Body and Stress Granule Components around Lipid Droplets
Authors: Ariumi Yasuo , Kuroki Misao , Kushima Yukihiro , Osugi Kanae , Hijikata Makoto , Maki Masatoshi , Ikeda Masanori , Kato Nobuyuki 
Published: May 2011

ABSTRACT
The microRNA miR-122 and DDX6/Rck/p54, a microRNA effector, have been implicated in hepatitis C virus (HCV) replication. In this study, we demonstrated for the first time that HCV-JFH1 infection disrupted processing (P)-body formation of the microRNA effectors DDX6, Lsm1, Xrn1, PATL1, and Ago2, but not the decapping enzyme DCP2, and dynamically redistributed these microRNA effectors to the HCV production factory around lipid droplets in HuH-7-derived RSc cells. Notably, HCV-JFH1 infection also redistributed the stress granule components GTPase-activating protein (SH3 domain)-binding protein 1 (G3BP1), ataxin-2 (ATX2), and poly(A)-binding protein 1 (PABP1) to the HCV production factory. In this regard, we found that the P-body formation of DDX6 began to be disrupted at 36 h postinfection. Consistently, G3BP1 transiently formed stress granules at 36 h postinfection. We then observed the ringlike formation of DDX6 or G3BP1 and colocalization with HCV core after 48 h postinfection, suggesting that the disruption of P-body formation and the hijacking of P-body and stress granule components occur at a late step of HCV infection. Furthermore, HCV infection could suppress stress granule formation in response to heat shock or treatment with arsenite. Importantly, we demonstrate that the accumulation of HCV RNA was significantly suppressed in DDX6, Lsm1, ATX2, and PABP1 knockdown cells after the inoculation of HCV-JFH1, suggesting that the P-body and the stress granule components are required for the HCV life cycle. Altogether, HCV seems to hijack the P-body and the stress granule components for HCV replication.
1-Hexyl n-cyanoacrylate compound (Neucrylate™ AN), a new berry aneurysm treatment. I. Theoretical basis and laboratory evaluation
Authors: Kerber Charles W , Pakbaz Ramin Sean 
Published: May 2011

PurposeTo develop and optimize a system for treating cerebral berry aneurysm using a new polymer based liquid embolic agent.Materials and methodsUsing a variety of human corrosion casting aneurysm replicas placed in a circuit of pulsatile flowing blood, techniques were developed to optimize aneurysm filling and recreate good blood flow dynamics. As part of this effort, both experienced physicians and lay personnel were asked to treat these replicas to discover common failure modes. Additional surgically created aneurysms in dog carotid arteries were treated by experienced physicians.ResultsPhysicians experienced in the use of microcatheters and endovascular techniques learned to use the device effectively after, on average, five aneurysm treatments. In the dog aneurysms, all were treated to complete filling.
Racial and Ethnic Disparities in Colorectal Cancer Screening Persisted Despite Expansion of Medicare's Screening Reimbursement
Authors: White Arica , Vernon Sally W. , Franzini Luisa , Du Xianglin L. 
Published: May 2011

Abstract
Objective: We examined the effect of Medicare's expansion of colorectal cancer (CRC) screening test reimbursement on racial/ethnic disparities in CRC screening.
Methods: CRC screening was ascertained for Medicare beneficiaries (n = 30,893), aged 70 to 89, who had no history of any tumor and resided in 16 Surveillance, Epidemiology and End Results regions of the United States from 1996 to 2005. CRC screening tests were identified in the 5% sample of Medicare claims. Age–gender-adjusted percentages and -adjusted odds of receiving any guideline-specific CRC screening [i.e., annual fecal occult blood test (FOBT), sigmoidoscopy every 5 years or colonoscopy every 10 years] by race/ethnicity and Medicare coverage expansion period (i.e., prior to FOBT coverage, FOBT coverage only, and post–colonoscopy coverage) were reported.
Results: CRC screening increased as Medicare coverage expanded for white and black Medicare beneficiaries. However, blacks were less likely than whites to receive screening prior to FOBT coverage (OR = 0.74, 95% CI: 0.61–0.90), during FOBT coverage only (OR = 0.66, 95% CI: 0.52–0.83) and after colonoscopy coverage (OR = 0.80, 95% CI: 0.68–0.95). Hispanics were less likely to receive screening after colonoscopy coverage (OR = 0.73, 95% CI: 0.54–0.99).
Conclusions: Despite the expansion of Medicare coverage for CRC screening tests, racial/ethnic differences in CRC screening persisted over time in this universally insured population, especially for blacks and Hispanics. Future studies should explore other factors beyond health insurance that may contribute to screening disparities in this and younger populations.
Impact: Although CRC screening rates increased over time, they were still low according to recommendations. More effort is needed to increase CRC screening among all Medicare beneficiaries. Cancer Epidemiol Biomarkers Prev; 20(5); 811–7. ©2011 AACR.
Prediagnostic Circulating Parathyroid Hormone Concentration and Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition Cohort
Authors: Fedirko Veronika , Riboli Elio , Bueno-de-Mesquita H. Bas , Rinaldi Sabina , Pischon Tobias , Norat Teresa , Jansen Eugène H. J. M. , van Duijnhoven Fränzel J. B. , Tjønneland Anne , Olsen Anja , Overvad Kim , Boutron-Ruault Marie-Christine , Clavel-Chapelon Françoise , Engel Pierre , Kaaks Rudolf , Teucher Birgit , Boeing Heiner , Buijsse Brian , Trichopoulou Antonia , Trichopoulos Dimitrios , Lagiou Pagona , Sieri Sabina , Vineis Paolo , Panico Salvatore , Palli Domenico , Tumino Rosario , van Gils Carla H. , Peeters Petra H. M. , Chirlaque Maria-Dolores , Gurrea Aurelio Barricarte , Rodríguez Laudina , Molina-Montes Esther , Dorronsoro Miren , Bonet Catalina , Palmqvist Richard , Hallmans Göran , Key Timothy J. , Tsilidis Konstantinos K , Khaw Kay-Tee , Romieu Isabelle , Straif Kurt , Wark Petra A. , Romaguera Dora , Jenab Mazda 
Published: May 2011

AbstractBackground: Parathyroid hormone (PTH) has been proposed to play a promoting role in carcinogenesis. However, no epidemiologic studies have yet directly investigated its role in colorectal cancer (CRC).Methods: A case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort was conducted with 1,214 incident, sporadic CRC cases matched to 1,214 controls. Circulating prediagnostic PTH and 25-hydroxy vitamin D [25(OH)D] concentrations were measured by enzyme-linked immunosorbent assays. Detailed dietary and lifestyle questionnaire data were collected at baseline. Multivariable conditional logistic regression was used to estimate the incidence rate ratio (RR) with 95% confidence intervals (95% CI) for the association between circulating PTH and CRC risk.Results: In multivariate analyses [including adjustment for 25(OH)D concentration] with a priori defined cutoff points, high levels of serum PTH (≥65 ng/L) compared with medium PTH levels of 30–65 ng/L were associated with increased CRC risk (RR = 1.41, 95% CI: 1.03–1.93). In analyses by sex, the CRC risk was 1.77 (95% CI: 1.14–2.75) and 1.15 (95% CI: 0.73–1.84) in men and women, respectively (Pheterogeneity = 0.01). In subgroup analyses by anatomical subsite, the risk for colon cancer was RR = 1.56, 95% CI: 1.03–2.34, and for rectal cancer RR = 1.20, 95% CI: 0.72–2.01 (Pheterogeneity = 0.21). Effect modification by various risk factors was examined.Conclusions: The results of this study suggest that high serum PTH levels may be associated with incident, sporadic CRC in Western European populations, and in particular among men.Impact: To our knowledge, this is the first study on PTH and CRC. The role of PTH in carcinogenesis needs to be further investigated. Cancer Epidemiol Biomarkers Prev; 20(5); 767–78. ©2011 AACR.
Reversals of Association for Pap, Colorectal, and Prostate Cancer Testing among Hispanic and Non-Hispanic Black Women and Men
Authors: Rakowski William , Clark Melissa A. , Rogers Michelle L. , Weitzen Sherry H. 
Published: May 2011

Abstract
Background: Several studies have found that Hispanics and non-Hispanic blacks have statistically significantly higher adjusted OR for cancer screening tests compared to non-Hispanic whites, even though their crude percentages were lower than, or about equal to, those for the non-Hispanic whites. Most documentation is for mammography. This article investigates the prevalence of such unadjusted-to-adjusted “reversed associations” (RA) for Pap, colorectal, and prostate testing. We also investigate large percent changes (LPC) to the unadjusted ORs.
Methods: Data were from the 2004/2006/2008 Behavioral Risk Factor Surveillance System (BRFSS) and the 2000/2003/2005/2008 National Health Interview Survey (NHIS). Analyses used a consistent set of covariates.
Results: RAs were more common for non-Hispanic blacks than Hispanics, but Hispanics had a greater number of LPCs. RAs and LPCs occurred more often for Pap testing than colorectal and prostate testing. However, results from the BRFSS and NHIS were often not consistent.
Conclusions: Attention should be given to the National Breast and Cervical Cancer Early Detection Program, as well as public programs addressing other cancers, as possible contributors to RAs and LPCs. Hispanics may show more RAs in analyses of future data. Discrepancies between the BRFSS and the NHIS also must be recognized and explained.
Impact: This research highlights the need for vigilance regarding the results of analyses to identify race/ethnicity as a correlate of cancer screening. Results also direct attention to aspects of the results of multivariable analysis other than ORs and confidence intervals. Cancer Epidemiol Biomarkers Prev; 20(5); 876–89. ©2011 AACR.
Smoking, Secondhand Smoke, and Cotinine Levels in a Subset of EPIC Cohort
Authors: Baltar Valéria Troncoso , Xun Wei W. , Chuang Shu-Chun , Relton Caroline , Ueland Per Magne , Vollset Stein Emil , Midttun Øivind , Johansson Mattias , Slimani Nadia , Jenab Mazda , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Fagherazzi Guy , Kaaks Rudolf , Rohrmann Sabine , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , Boshuizen Hendriek C , van Gils Carla H. , Peeters Petra H.M. , Agudo Antonio , Barricarte Aurelio , Navarro Carmen , Rodríguez Laudina , Castaño José Maria Huerta , Larrañaga Nerea , Pérez Maria José Sánchez , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Crowe Francesca , Gallo Valentina , Norat Teresa , Tagliabue Giovanna , Masala Giovanna , Panico Salvatore , Sacerdote Carlota , Tumino Rosario , Trichopoulou Antonia , Lagiou Pagona , Bamia Christina , Rasmuson Torgny , Hallmans Göran , Roswall Nina , Tjønneland Anne , Riboli Elio , Brennan Paul , Vineis Paolo 
Published: May 2011

Abstract
Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index.
Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P &lt; 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P &lt; 0.001).
Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels.
Impact: This study strengthens the evidence for the benefits of a smoking ban in public places. Cancer Epidemiol Biomarkers Prev; 20(5); 869–75. ©2011 AACR.