bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C-Terminal Region of Lymphocytic Choriomeningitis Virus Nucleoprotein Contains Distinct and Segregable Functional Domains Involved in NP-Z Interaction and Counteraction of the Type I Interferon Response
Authors: Ortiz-Riaño Emilio , Cheng Benson Yee Hin , de la Torre Juan Carlos , Martínez-Sobrido Luis 
Published: October 2011

ABSTRACT
Several arenaviruses cause hemorrhagic fever (HF) disease in humans that is associated with high morbidity and significant mortality. Arenavirus nucleoprotein (NP), the most abundant viral protein in infected cells and virions, encapsidates the viral genome RNA, and this NP-RNA complex, together with the viral L polymerase, forms the viral ribonucleoprotein (vRNP) that directs viral RNA replication and gene transcription. Formation of infectious arenavirus progeny requires packaging of vRNPs into budding particles, a process in which arenavirus matrix-like protein (Z) plays a central role. In the present study, we have characterized the NP-Z interaction for the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). The LCMV NP domain that interacted with Z overlapped with a previously documented C-terminal domain that counteracts the host type I interferon (IFN) response. However, we found that single amino acid mutations that affect the anti-IFN function of LCMV NP did not disrupt the NP-Z interaction, suggesting that within the C-terminal region of NP different amino acid residues critically contribute to these two distinct and segregable NP functions. A similar NP-Z interaction was confirmed for the HF arenavirus Lassa virus (LASV). Notably, LCMV NP interacted similarly with both LCMV Z and LASV Z, while LASV NP interacted only with LASV Z. Our results also suggest the presence of a conserved protein domain within NP but with specific amino acid residues playing key roles in determining the specificity of NP-Z interaction that may influence the viability of reassortant arenaviruses. In addition, this NP-Z interaction represents a potential target for the development of antiviral drugs to combat human-pathogenic arenaviruses.
Microvesicles and Viral Infection
Authors: Meckes David G. , Raab-Traub Nancy 
Published: October 2011

ABSTRACTCells secrete various membrane-enclosed microvesicles from their cell surface (shedding microvesicles) and from internal, endosome-derived membranes (exosomes). Intriguingly, these vesicles have many characteristics in common with enveloped viruses, including biophysical properties, biogenesis, and uptake by cells. Recent discoveries describing the microvesicle-mediated intercellular transfer of functional cellular proteins, RNAs, and mRNAs have revealed additional similarities between viruses and cellular microvesicles. Apparent differences include the complexity of viral entry, temporally regulated viral expression, and self-replication proceeding to infection of new cells. Interestingly, many virally infected cells secrete microvesicles that differ in content from their virion counterparts but may contain various viral proteins and RNAs. For the most part, these particles have not been analyzed for their content or functions during viral infection. However, early studies of microvesicles (L-particles) secreted from herpes simplex virus-infected cells provided the first evidence of microvesicle-mediated intercellular communication. In the case of Epstein-Barr virus, recent evidence suggests that this tumorigenic herpesvirus also utilizes exosomes as a mechanism of cell-to-cell communication through the transfer of signaling competent proteins and functional microRNAs to uninfected cells. This review focuses on aspects of the biology of microvesicles with an emphasis on their potential contributions to viral infection and pathogenesis.
Spring-Loaded Model Revisited: Paramyxovirus Fusion Requires Engagement of a Receptor Binding Protein beyond Initial Triggering of the Fusion Protein
Authors: Porotto Matteo , DeVito Ilaria , Palmer Samantha G. , Jurgens Eric M. , Yee Jia L. , Yokoyama Christine C. , Pessi Antonello , Moscona Anne 
Published: October 2011

ABSTRACT
During paramyxovirus entry into a host cell, receptor engagement by a specialized binding protein triggers conformational changes in the adjacent fusion protein (F), leading to fusion between the viral and cell membranes. According to the existing paradigm of paramyxovirus membrane fusion, the initial activation of F by the receptor binding protein sets off a spring-loaded mechanism whereby the F protein progresses independently through the subsequent steps in the fusion process, ending in membrane merger. For human parainfluenza virus type 3 (HPIV3), the receptor binding protein (hemagglutinin-neuraminidase [HN]) has three functions: receptor binding, receptor cleaving, and activating F. We report that continuous receptor engagement by HN activates F to advance through the series of structural rearrangements required for fusion. In contrast to the prevailing model, the role of HN-receptor engagement in the fusion process is required beyond an initiating step, i.e., it is still required even after the insertion of the fusion peptide into the target cell membrane, enabling F to mediate membrane merger. We also report that for Nipah virus, whose receptor binding protein has no receptor-cleaving activity, the continuous stimulation of the F protein by a receptor-engaged binding protein is key for fusion. We suggest a general model for paramyxovirus fusion activation in which receptor engagement plays an active role in F activation, and the continued engagement of the receptor binding protein is essential to F protein function until the onset of membrane merger. This model has broad implications for the mechanism of paramyxovirus fusion and for strategies to prevent viral entry.
Phylogenetic Analysis of H6 Influenza Viruses Isolated from Rosy-Billed Pochards (Netta peposaca) in Argentina Reveals the Presence of Different HA Gene Clusters
Authors: Rimondi Agustina , Xu Kemin , Craig Maria Isabel , Shao Hongxia , Ferreyra Hebe , Rago Maria Virginia , Romano Marcelo , Uhart Marcela , Sutton Troy , Ferrero Andrea , Perez Daniel R. , Pereda Ariel 
Published: October 2011

ABSTRACT

Until recently, influenza A viruses from wild waterfowl in South America were rarely isolated and/or characterized. To explore the ecology of influenza A viruses in this region, a long-term surveillance program was established in 2006 for resident and migratory water birds in Argentina. We report the characterization of 5 avian influenza viruses of the H6 hemagglutinin (HA) subtype isolated from rosy-billed pochards (
Netta peposaca
). Three of these viruses were paired to an N2 NA subtype, while the other two were of the N8 subtype. Genetic and phylogenetic analyses of the internal gene segments revealed a close relationship with influenza viruses from South America, forming a unique clade and supporting the notion of independent evolution from influenza A viruses in other latitudes. The presence of NS alleles A and B was also identified. The HA and NA genes formed unique clades separate from North American and Eurasian viruses, with the exception of the HA gene of one isolate, which was more closely related to the North American lineage, suggesting possible interactions between viruses of North American and South American lineages. Animal studies suggested that these Argentine H6 viruses could replicate and transmit inefficiently in chickens, indicating limited adaptation to poultry. Our results highlight the importance of continued influenza virus surveillance in wild birds of South America, especially considering the unique evolution of these viruses.
A Murine Genital-Challenge Model Is a Sensitive Measure of Protective Antibodies against Human Papillomavirus Infection
Authors: Longet Stéphanie , Schiller John T. , Bobst Martine , Jichlinski Patrice , Nardelli-Haefliger Denise 
Published: October 2011

ABSTRACT

The available virus-like particle (VLP)-based prophylactic vaccines against specific human papillomavirus (HPV) types afford close to 100% protection against the type-associated lesions and disease. Based on papillomavirus animal models, it is likely that protection against genital lesions in humans is mediated by HPV type-restricted neutralizing antibodies that transudate or exudate at the sites of genital infection. However, a correlate of protection was not established in the clinical trials because few disease cases occurred, and true incident infection could not be reliably distinguished from the emergence or reactivation of prevalent infection. In addition, the current assays for measuring vaccine-induced antibodies, even the gold standard HPV pseudovirion (PsV)
in vitro
neutralization assay, may not be sensitive enough to measure the minimum level of antibodies needed for protection. Here, we characterize the recently developed model of genital challenge with HPV PsV and determine the minimal amounts of VLP-induced neutralizing antibodies that can afford protection from genital infection
in vivo
after transfer into recipient mice. Our data show that serum antibody levels >100-fold lower than those detectable by
in vitro
PsV neutralization assays are sufficient to confer protection against an HPV PsV genital infection in this model. The results clearly demonstrate that, remarkably, the
in vivo
assay is substantially more sensitive than
in vitro
PsV neutralization and thus may be better suited for studies to establish correlates of protection.
Long-term Safety of Radiotherapy and Breast Cancer Laterality in Older Survivors
Authors: Haque Reina , Yood Marianne Ulcickas , Geiger Ann M. , Kamineni Aruna , Avila Chantal C. , Shi Jiaxiao , Silliman Rebecca A. , Quinn Virginia P. 
Published: October 2011

Abstract
Background: Although adjuvant radiotherapy (RT) following surgery for breast cancer improves overall survival, controversy exists about its long-term adverse impact on cardiovascular health in older survivors.
Aim: To determine whether incident cardiovascular disease (CVD) is associated with RT and whether tumor laterality modifies this association.
Methods: Women aged 65+ years diagnosed with stage I and II breast cancer between 1990 and 1994 were identified from three health plans. Women were followed through CVD outcomes, health plan disenrollment, death, or study end (December 31, 2004). The main independent variable was RT use. Adjusted HRs and 95% CIs were estimated using Cox proportional hazards models with time-dependent tamoxifen and RT use status. We adjusted for age, race, stage, estrogen receptor/progesterone receptor, hypertension, and diabetes.
Results: In the full cohort (N = 806), RT was not associated with greater risk of CVD (maximum follow-up was 14 years). However, within the RT-exposed group (N = 340), women treated for left-side breast cancer had a significant increased risk of CVD outcomes (HR = 1.53, 95% CI: 1.06–2.21) compared with women with right-sided tumors.
Conclusion: Laterality is critical to understanding the effect of RT on CVD. Studies of more contemporary cohorts of women treated with RT should incorporate this variable to determine whether the risk persists with refinements in the dosing and delivery of RT.
Impact: As some irradiation to the heart is unavoidable even with refined modern RT techniques, continued effort is required to minimize such exposures, especially in older women with left-sided tumors. Cancer Epidemiol Biomarkers Prev; 20(10); 2120–6. ©2011 AACR.
Cancer Fatalism and Poor Self-Rated Health Mediate the Association between Socioeconomic Status and Uptake of Colorectal Cancer Screening in England
Authors: Miles Anne , Rainbow Sandra , von Wagner Christian 
Published: October 2011

AbstractBackground: Little is known about the psychological predictors of colorectal screening uptake in England and mediators of associations between uptake and socioeconomic status (SES). This study tested the hypotheses that although higher threat and efficacy beliefs, lower cancer fatalism, lower depression, and better self-rated health would predict higher screening uptake, only efficacy beliefs, fatalism, depression, and self-rated health would mediate associations between uptake and SES.Methods: Data from 529 adults aged 60 to 69 who had completed a postal survey in 2005–2006 were linked with data on fecal occult blood test (FOBt) uptake recorded at the screening “hub” following its introduction in 2007, resulting in a prospective study.Results: Screening uptake was 56% and was higher among people with higher SES, better self-rated health, higher self-efficacy beliefs, and lower cancer fatalism in univariate analyses. Path analysis on participants with complete data (n = 515) showed that both better self-rated health and lower cancer fatalism were directly associated with higher uptake of FOBt screening and significantly mediated pathways from SES to uptake. Lower depression only had an indirect effect on uptake through better self-rated health. Efficacy beliefs did not mediate the relationship between SES and uptake.Conclusion: SES differences in uptake of FOBt in England are partially explained by differences in cancer fatalism, self-rated health, and depression.Impact: This is one of only a few studies to examine mediators of the relationship between SES and screening uptake, and future research could test the effectiveness of interventions to reduce fatalistic beliefs to increase equality of uptake. Cancer Epidemiol Biomarkers Prev; 20(10); 2132–40. ©2011 AACR.
Stage at Diagnosis and Comorbidity Influence Breast Cancer Survival in First Nations Women in Ontario, Canada
Authors: Sheppard Amanda J. , Chiarelli Anna M. , Marrett Loraine D. , Nishri E. Diane , Trudeau Maureen E. 
Published: October 2011

Abstract
Background: Indigenous populations in Canada and abroad have poorer survival after a breast cancer diagnosis compared with their geographic counterparts; however, the influence of many demographic, personal, tumor, and treatment factors has not been examined to describe this disparity according to stage at diagnosis.
Methods: A case–case design was employed to compare First Nations (FN) women (n = 287) to a frequency-matched random sample of non-FN women (n = 671) diagnosed with breast cancer within the Ontario Cancer Registry. Women were matched on period of diagnosis (1995–1999 and 2000–2004), age at diagnosis (&lt;50 vs. ≥50), and Regional Cancer Centre (RCC). Stage and other factors were collected from medical charts at the RCCs. Survival was compared using an adjusted Cox proportional hazards model and stratified by stage at diagnosis (I, II, and III–IV). Determinants of survival in FN women stratified by stage at diagnosis were also modeled.
Results: Survival was more than three times poorer for FN women diagnosed at stage I than for non-FN women (HR = 3.10, 95% CI = 1.39–6.88). The risk of death after a stage I breast cancer diagnosis was about five times higher among FN women with a comorbidity other than diabetes (HR = 4.65, 95% CI = 1.39–15.53) and was more than five times greater for women with diabetes (HR = 5.49, 95% CI = 1.69–17.90) than for those without a comorbidity.
Conclusions: Having a preexisting comorbidity was the most important factor in explaining the observed survival disparity among FN women.
Impact: Improving the general health status of FN women could increase their survival after an early-stage breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev; 20(10); 2160–7. ©2011 AACR.
Vitamin, Mineral, and Specialty Supplements and Risk of Hematologic Malignancies in the Prospective VITamins And Lifestyle (VITAL) Study
Authors: Walter Roland B. , Brasky Theodore M. , Milano Filippo , White Emily 
Published: October 2011

AbstractBackground: Increasing evidence suggests that nutrients from fruits and vegetables have chemoprotective effects on various cancers including hematologic malignancies, but the effects of nutritional supplements are poorly examined.Methods: Herein, we prospectively evaluated the association of vitamin, mineral, and specialty supplements with incident hematologic malignancies in 66,227 men and women aged 50 to 76 years from Washington State recruited from year 2000 to 2002 to the VITamins And Lifestyle (VITAL) cohort study. Hematologic malignancies cases (n = 588) were identified through December 2008 by linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. HRs and 95% CIs associated with supplement use were estimated with Cox proportional hazards models.Results: After adjustment, high use of garlic supplements [≥4 days per week for ≥3 years; HR = 0.55 (95% CI = 0.34–0.87); Ptrend = 0.028] and ever use of grape seed supplements [HR = 0.57 (95% CI = 0.37–0.88)] were inversely associated with hematologic malignancies in our models. In addition, high use (8–10 pill-years) of multivitamins was suggestive of an inverse association [HR = 0.80 (95% CI = 0.64–1.01)]. In contrast, no associations were observed for the remaining supplements.Conclusions: These data indicate that the use of garlic and grape seed may be associated with reduced risk of hematologic malignancies.Impact: This is the first cohort study to suggest a possible role of these supplements in the chemoprevention of hematologic malignancies. Cancer Epidemiol Biomarkers Prev; 20(10); 2298–308. ©2011 AACR.
Genetic Polymorphisms in 15q25 and 19q13 Loci, Cotinine Levels, and Risk of Lung Cancer in EPIC
Authors: Timofeeva Maria N. , McKay James D. , Davey Smith George , Johansson Mattias , Byrnes Graham B. , Chabrier Amélie , Relton Caroline , Ueland Per Magne , Vollset Stein Emil , Midttun Øivind , Nygård Ottar , Slimani Nadia , Romieu Isabelle , Clavel-Chapelon Françoise , Boutron-Ruault Marie-Christine , Fagherazzi Guy , Kaaks Rudolf , Teucher Birgit , Boeing Heiner , Weikert Cornelia , Bueno-de-Mesquita H. Bas , van Gils Carla , Peeters Petra H.M. , Agudo Antonio , Barricarte Aurelio , Huerta Jose-Maria , Rodríguez Laudina , Sánchez Maria-José , Larrañaga Nerea , Khaw Kay-Tee , Wareham Nick , Allen Naomi E. , Travis Ruth C. , Gallo Valentina , Norat Teresa , Krogh Vittorio , Masala Giovanna , Panico Salvatore , Sacerdote Carlotta , Tumino Rosario , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Rasmuson Torgny , Hallmans Göran , Riboli Elio , Vineis Paolo , Brennan Paul 
Published: October 2011

Abstract
Backgrounds: Multiple polymorphisms affecting smoking behavior have been identified through genome-wide association studies. Circulating levels of the nicotine metabolite cotinine is a marker of recent smoking exposure. Hence, genetic variants influencing smoking behavior are expected to be associated with cotinine levels.
Methods: We conducted an analysis in a lung cancer case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We investigated the effects of single-nucleotide polymorphisms (SNP) previously associated with smoking behavior on (i) circulating cotinine and (ii) lung cancer risk. A total of 894 cases and 1,805 controls were analyzed for cotinine and genotyped for 10 polymorphisms on 7p14, 8p11, 10q23, 15q25, and 19q13.
Results: Two variants in the nicotinic acetylcholine receptor subunit genes CHRNA5 and CHRNA3 on 15q25, rs16969968 and rs578776, were associated with cotinine (P = 0.001 and 0.03, respectively) in current smokers and with lung cancer risk (P &lt; 0.001 and P = 0.001, respectively). Two 19q13 variants, rs7937 and rs4105144, were associated with increased cotinine (P = 0.003 and P &lt; 0.001, respectively) but decreased lung cancer risk (P = 0.01 for both, after adjusting for cotinine). Variants in 7p14, 8p11, and 10q23 were not associated with cotinine or lung cancer risk.
Conclusions: 15q25 and 19q13 SNPs were associated with circulating cotinine. The directions of association for 15q25 variants with cotinine were in accordance with that expected of lung cancer risk, whereas SNPs on 19q13 displayed contrasting associations of cotinine and lung cancer that require further investigation.
Impact: This study is the largest to date investigating the effects of polymorphisms affecting smoking behavior on lung cancer risk using circulating cotinine measures as proxies for recent smoking behavior. Cancer Epidemiol Biomarkers Prev; 20(10); 2250–61. ©2011 AACR.
Analysis of cagA in Helicobacter pylori Strains from Colombian Populations with Contrasting Gastric Cancer Risk Reveals a Biomarker for Disease Severity
Authors: Loh John T. , Shaffer Carrie L. , Piazuelo M. Blanca , Bravo Luis E. , McClain Mark S. , Correa Pelayo , Cover Timothy L. 
Published: October 2011

Abstract
Background: Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis.
Methods: We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain.
Results: A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif.
Conclusions: CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk.
Impact: These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not. Cancer Epidemiol Biomarkers Prev; 20(10); 2237–49. ©2011 AACR.
Predictors of Breast Density Change After Hormone Therapy Cessation: Results from a Randomized Trial
Authors: Lowry Sarah J. , Aiello Bowles Erin J. , Anderson Melissa L. , Buist Diana S.M. 
Published: October 2011

Abstract
Background: Postmenopausal hormone therapy cessation is associated with a decrease in mammographic density (MD), but it is unknown whether this effect is modified by woman-level characteristics. We investigated whether we could identify characteristics of women who were most likely to experience a decrease in MD due to hormone therapy cessation.
Methods: Postmenopausal hormone therapy users with a prior screening mammogram (n = 1,168) were randomized to continue hormone therapy or to suspend hormone therapy for 1 month or 2 months before their next screening mammogram. We estimated relative risks (RR) and attributable risks with 95% CIs of a ≥7.5% decrease in percentage MD (%MD) versus no change associated with hormone therapy cessation, stratified by age, body mass index (BMI), parity, and other factors.
Results: Hormone therapy cessation increased a woman's likelihood of experiencing a ≥7.5% decrease in %MD by 30% (95% CI = 1.03–1.7), but we found little evidence of effect modification by age, race, BMI, change in BMI, baseline %MD, parity, family history of breast cancer, hormone therapy type, or duration of hormone therapy use.
Conclusions: Woman-level factors do not appear to explain why some women experience a decrease in %MD following hormone therapy cessation and others do not.
Impact: We were unable to identify subgroups of women who are more likely to experience a decrease in MD due to hormone therapy cessation; other factors, such as genetic factors, may be important determinants of hormone therapy–related changes in MD. Cancer Epidemiol Biomarkers Prev; 20(10); 2309–12. ©2011 AACR.