bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Latent Membrane Protein 1 Regulates the Function of Interferon Regulatory Factor 7 by Inducing Its Sumoylation
Authors: Bentz Gretchen L. , Shackelford Julia , Pagano Joseph S. 
Published: September 2012

ABSTRACT
Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) induces multiple signal transduction pathways during latent EBV infection via its C-terminal activating region 1 (CTAR1), CTAR2, and the less-studied CTAR3. One mechanism by which LMP1 regulates cellular activation is through the induction of protein posttranslational modifications, including phosphorylation and ubiquitination. We recently documented that LMP1 induces a third major protein modification by physically interacting with the SUMO-conjugating enzyme Ubc9 through CTAR3 and inducing the sumoylation of cellular proteins in latently infected cells. We have now identified a specific target of LMP1-induced sumoylation, interferon regulatory factor 7 (IRF7). We hypothesize that during EBV latency, LMP1 induces the sumoylation of IRF7, limiting its transcriptional activity and modulating the activation of innate immune responses. Our data show that endogenously sumoylated IRF7 is detected in latently infected EBV lymphoblastoid cell lines. LMP1 expression coincided with increased sumoylation of IRF7 in a CTAR3-dependent manner. Additional experiments show that LMP1 CTAR3-induced sumoylation regulates the expression and function of IRF7 by decreasing its turnover, increasing its nuclear retention, decreasing its DNA binding, and limiting its transcriptional activation. Finally, we identified that IRF7 is sumoylated at lysine 452. These data demonstrate that LMP1 CTAR3 does in fact function in intracellular signaling, leading to biologic effects. We propose that CTAR3 is an important signaling region of LMP1 that regulates protein function by sumoylation. We have shown specifically that LMP1 CTAR3, in cooperation with CTAR2, can limit the ability of IRF7 to induce innate immune responses by inducing the sumoylation of IRF7.
The Asian-American E6 Variant Protein of Human Papillomavirus 16 Alone Is Sufficient To Promote Immortalization, Transformation, and Migration of Primary Human Foreskin Keratinocytes
Authors: Niccoli Sarah , Abraham Suraj , Richard Christina , Zehbe Ingeborg 
Published: September 2012

ABSTRACT

We examined how well the human papillomavirus (HPV) E6 oncogene can function in the absence of the E7 oncogene during the carcinogenic process in human keratinocytes using a common HPV variant strongly associated with cervical cancer: the Asian-American E6 variant (AAE6). This E6 variant is 20 times more frequently detected in cervical cancer than the prototype European E6 variant, as evidenced by independent epidemiological data. Using cell culture and cell-based functional assays, we assessed how this variant can perform crucial carcinogenesis steps compared to the prototype E6 variant. The ability to immortalize and transform primary human foreskin keratinocytes (PHFKs) to acquire resilient phenotypes and the ability to promote cell migration were evaluated. The immortalization capability was assayed based on population doublings, number of passages, surpassing mortality stages 1 and 2, human telomerase reverse transcriptase (hTERT) expression, and the ability to overcome G
1
arrest via p53 degradation. Transformation and migration efficiency were analyzed using a combination of functional cell-based assays. We observed that either AAE6 or prototype E6 proteins alone were sufficient to immortalize PHFKs, although AAE6 was more potent in doing so. The AAE6 variant protein alone pushed PHFKs through transformation and significantly increased their migration ability over that of the E6 prototype. Our findings are in line with epidemiological data that the AA variant of HPV16 confers an increased risk over the European prototype for cervical cancer, as evidenced by a superior immortalization, transformation, and metastatic potential.
Oligomeric Recombinant H5 HA1 Vaccine Produced in Bacteria Protects Ferrets from Homologous and Heterologous Wild-Type H5N1 Influenza Challenge and Controls Viral Loads Better than Subunit H5N1 Vaccine by Eliciting High-Affinity Antibodies
Authors: Verma Swati , Dimitrova Milena , Munjal Ashok , Fontana Juan , Crevar Corey J. , Carter Donald M. , Ross Ted M. , Khurana Surender , Golding Hana 
Published: September 2012

ABSTRACT
Recombinant hemagglutinin from influenza viruses with pandemic potential can be produced rapidly in various cell substrates. In this study, we compared the functionality and immunogenicity of bacterially produced oligomeric or monomeric HA1 proteins from H5N1 (A/Vietnam/1203/04) with those of the egg-based licensed subunit H5N1 (SU-H5N1) vaccine in ferrets challenged with homologous or heterologous H5N1 highly pathogenic influenza strains. Ferrets were vaccinated twice with the oligomeric or monomeric rHA1 or with SU-H5N1 (Sanofi Pasteur) emulsified with Titermax adjuvant and were challenged with wild-type homologous (A/Vietnam/1203/04; clade 1) or heterologous (A/Whooperswan/Mongolia/244/2005; clade 2.2) virus. Only the oligomeric rHA1 (not the monomeric rHA1) immunogen and the SU-H5N1 vaccine provided protection against the lethality and morbidity of homologous and heterologous highly pathogenic H5N1. Oligomeric rHA1 generated more cross-neutralizing antibodies and higher levels of serum antibody binding to HA1, with stronger avidity and a better IgG/IgM ratio, than monomeric HA1 and SU-H5N1 vaccines, as determined by surface plasmon resonance (SPR). Importantly, viral loads after heterologous H5N1 challenge were more efficiently controlled in ferrets vaccinated with the oligomeric rHA1 immunogen than in SU-H5N1-vaccinated ferrets. The reduction of viral loads in the nasal washes correlated strongly with higher-avidity antibodies to oligomeric rHA1 derived from H5N1 clade 1 and clade 2.2 viruses, as measured by SPR. This is the first study to show the role of antibody avidity for the HA1 globular head domain in reduction of viral loads in the upper respiratory tract, which could significantly reduce viral transmission.
Conserved Fiber-Penton Base Interaction Revealed by Nearly Atomic Resolution Cryo-Electron Microscopy of the Structure of Adenovirus Provides Insight into Receptor Interaction
Authors: Cao Changchun , Dong Xiaoyan , Wu Xiaobing , Wen Boyun , Ji Gang , Cheng Lingpeng , Liu Hongrong 
Published: September 2012

ABSTRACT
Adenovirus (Ad) cell attachment is initiated by the attachment of the fiber protein to a primary receptor (usually CAR or CD46). This event is followed by the engagement of the penton base protein with a secondary receptor (integrin) via its loop region, which contains an Arg-Gly-Asp (RGD) motif, to trigger virus internalization. To understand the well-orchestrated adenovirus cell attachment process that involves the fiber and the penton base, we reconstructed the structure of an Ad5F35 capsid, comprising an adenovirus type 5 (Ad5) capsid pseudotyped with an Ad35 fiber, at a resolution of approximately 4.2 Å. The fiber-penton base interaction in the cryo-electron microscopic (cryo-EM) structure of Ad5F35 is similar to that in the cryo-EM structure of Ad5, indicating that the fiber-penton base interaction of adenovirus is conserved. Our structure also confirms that the C-terminal segment of the fiber tail domain constitutes the bottom trunk of the fiber shaft. Based on the conserved fiber-penton base interaction, we have proposed a model for the interaction of Ad5F35 with its primary and secondary receptors. This model could provide insight for designing adenovirus gene delivery vectors.
Mutations in the M-Gene Segment Can Substantially Increase Replication Efficiency of NS1 Deletion Influenza A Virus in MDCK Cells
Authors: van Wielink R. , Harmsen M. M. , Martens D. E. , Peeters B. P. H. , Wijffels R. H. , Moormann R. J. M. 
Published: September 2012

ABSTRACT
Influenza viruses unable to express NS1 protein (delNS1) replicate poorly and induce large amounts of interferon (IFN). They are therefore considered candidate viruses for live-attenuated influenza vaccines. Their attenuated replication is generally assumed to result from the inability to counter the antiviral host response, as delNS1 viruses replicate efficiently in Vero cells, which lack IFN expression. In this study, delNS1 virus was parallel passaged on IFN-competent MDCK cells, which resulted in two strains that were able to replicate to high virus titers in MDCK cells due to adaptive mutations especially in the M-gene segment but also in the NP and NS gene segments. Most notable were clustered U-to-C mutations in the M segment of both strains and clustered A-to-G mutations in the NS segment of one strain, which presumably resulted from host cell-mediated RNA editing. The M segment mutations in both strains changed the ratio of M1 to M2 expression, probably by affecting splicing efficiency. In one virus, 2 amino acid substitutions in M1 additionally enhanced virus replication, possibly through changes in the M1 distribution between the nucleus and the cytoplasm. Both adapted viruses induced levels of IFN equal to that of the original delNS1 virus. These results show that the increased replication of the adapted viruses is not primarily due to altered IFN induction but rather is related to changes in M1 expression or localization. The mutations identified in this paper may be used to enhance delNS1 virus replication for vaccine production.
Patterns in wireless phone estimation data from a cross-sectional survey: what are the implications for epidemiology?
Authors: Redmayne Mary , Smith Euan , Abramson Michael J 
Published: September 2012

ObjectiveSelf-reported recall data are often used in wireless phone epidemiological studies, which in turn are used to indicate relative risk of health outcomes from extended radiofrequency exposure. We sought to explain features commonly observed in wireless phone recall data and to improve analytical procedures.SettingWellington Region, New Zealand.ParticipantsEach of the 16 schools selected a year 7 and/or 8 class to participate, providing a representative regional sample based on socioeconomic school ratings, school type and urban/rural balance. There was an 85% participation rate (N=373).Main outcome measuresPlanned: the distribution of participants’ estimated extent of SMS-texting and cordless phone calls, and the extent of rounding to a final zero or five within the full set of recall data and within each order of magnitude. Unplanned: the distribution of the leading digits of these raw data, compared with that of billed data in each order of magnitude.ResultsThe nature and extent of number-rounding, and the distribution of data acrosseachorder in recall data indicated a logarithmic (ratio-based) mental process for assigning values. Responses became less specific as the leading-digit increased from 1 to 9, and 69% of responses for weekly texts sent were rounded by participants to a single non-zero digit (eg, 2, 20 and 200).ConclusionsAdolescents’ estimation of their cellphone use indicated that it was performed on a mental logarithmic scale. This is the first time this phenomenon has been observed in the estimation of recalled, as opposed to observed, numerical quantities. Our findings provide empirical justification for log-transforming data for analysis. We recommend the use of the geometric rather than arithmetic mean when a recalled numerical range is provided. A point of calibration may improve recall.
Carers’ perspectives on the presentation of community-acquired pneumonia and empyema in children: a case series
Authors: Crocker Joanna C , Evans Meirion R , Butler Christopher C , Hood Kerenza , Powell Colin V E 
Published: September 2012

ObjectiveTo describe carers’ perceptions of the development and presentation of community-acquired pneumonia or empyema in their children.DesignCase series.SettingSeven hospitals with paediatric inpatient units in South Wales, UK.ParticipantsCarers of 79 children aged 6 months to 16 years assessed in hospital between October 2008 and September 2009 with radiographic, community-acquired pneumonia or empyema.MethodsCarers were recruited in hospital and participated in a structured face-to-face or telephone interview about the history and presenting features of their children's illnesses. Responses to open questions were initially coded very finely and then grouped into common themes. Cases were classified into two age groups: 3 or more years and under 3 years.ResultsThe reported median duration of illness from onset until the index hospital presentation was 4 days (IQR 2–9 days). Pain in the torso was reported in 84% of cases aged 3 or more years and was the most common cause for carer concern in this age group. According to carer accounts, clinicians sometimes misjudged the origin of this pain. Almost all carers reported something unusual about the index illness that had particularly concerned them—mostly non-specific physical symptoms and behavioural changes.ConclusionsPain in the torso and carer concerns about unusual symptoms in their child may provide valuable additional information in a clinician's assessment of the risk of pneumonia in primary care. Further research is needed to confirm the diagnostic value of these features.
Public perceptions of coronary events risk factors: a discrete choice experiment
Authors: Al Hamarneh Yazid N , Agus Ashley , Campbell Danny , Crealey Grainne E , McElnay James C 
Published: September 2012

ObjectivesTo assess public perceptions of coronary heart disease (CHD) risk factors.DesignDiscrete choice experiment questionnaire.SettingSix provincial centres in Northern Ireland.Participants1000 adults of the general public in Northern Ireland.Primary and secondary outcomesThe general public's perception of CHD risk factors. The effect of having risk factor(s) on that perception.ResultsTwo multinomial logit models were created. One was a basic model (no heterogeneity permitted), while the other permitted heterogeneity based on respondents’ characteristics. In both models individuals with very high cholesterol were perceived to be at the highest risk of having a coronary event. Respondents who reported having high cholesterol perceived the risk contribution of very high cholesterol to be greater than those who reported having normal cholesterol. Similar findings were observed with blood pressure and smoking. Respondents who were male and older perceived the contribution of age and gender to be lower than respondents who were female and younger.ConclusionsRespondents with different risk factors perceived such factors differently. These divergent perceptions of CHD risk factors could be a barrier to behavioural change. This brings into focus the need for more tailored health promotion campaigns to tackle CHD.
Collaborative palliative care for advanced heart failure: outcomes and costs from the ‘Better Together’ pilot study
Authors: Pattenden Jill F , Mason Anne R , Lewin R J P 
Published: September 2012

BackgroundPatients with heart failure often receive little supportive or palliative care. ‘Better Together’ was a 2-year pilot study of a palliative care service for patients with advanced congestive heart failure (CHF).ObjectiveTo determine if the intervention made it more likely that patients would be cared for and die in their place of choice, and to investigate its cost-effectiveness.MethodsThis pragmatic non-randomised pilot evaluation was set in two English primary care trusts (Bradford and Poole). Prospective patient-level data on outcomes and costs were compared with data from a historical control group of clinically comparable patients. Outcomes included death in preferred place of care (available only for the intervention group) and ‘hospital admissions averted’. Costs included medical procedures, inpatient care and the direct cost of providing the intervention.Results99 patients were referred. Median survival from referral was 48 days in Bradford and 31 days in Poole. Most patients who died did so in their preferred place of death (Bradford 70%, Poole 77%). An estimated 14 and 18 hospital admissions for heart failure were averted in Bradford and Poole, respectively. The average cost-per-heart failure admission averted was £1529 in Bradford, but the intervention was cost saving in Poole. However, there was considerable uncertainty around these cost-effectiveness estimates.ConclusionsThis pilot study provides tentative evidence that a collaborative home-based palliative care service for patients with advanced CHF may increase the likelihood of death in place of choice and reduce inpatient admissions. These findings require confirmation using a more robust methodological framework.
Dual-porosity fractured Miocene syn-rift dolomite reservoir in the Issaran Field (Gulf of Suez, Egypt): a case history of the zonal isolation of highly fractured water carrier bed
Authors: Saoudi Ati , Moustafa Adel R. , Farag Ramadan I. , Omara Maher M. , Wally Hossam , Fouad Ahmed , Tag Amr , Ragab Ramy Z. 
Published: September 2012

Abstract
We describe a fractured dolomite reservoir in the Miocene syn-rift succession of the Gulf of Suez, and the impact of fractures on the increase in the water cut during production from this reservoir and the measures taken to overcome this problem. The Issaran Field includes two dolomite reservoirs (the Upper and Lower Dolomite). The Lower Dolomite reservoir has a highly fractured zone (HFZ) corresponding to a brittle layer that extends down-dip below the highest know water level, allowing the flow of water from the water-wet area to other parts of the reservoir and, thus, causing an increase in the water cut in the wells. Setting an inflatable packer above the HFZ in open holes, perforation above its level in cased holes and reaching total depth of new wells above the HFZ are recommended to decrease the water cut. Accidental hydraulic fractures might develop by steam injection at pressures exceeding rock fracture pressure. These fractures and critically stressed natural fractures allow injected steam to pass laterally through the reservoir along interconnected natural fractures.
Cell-Cycle Control in Urothelial Carcinoma: Large-scale Tissue Array Analysis of Tumor Tissue from Maine and Vermont
Authors: Lenz Petra , Pfeiffer Ruth , Baris Dalsu , Schned Alan R. , Takikita Mikiko , Poscablo M. Cristina , Schwenn Molly , Johnson Alison , Jones Michael , Kida Masatoshi , Cantor Kenneth P. , Rothman Nathaniel , Silverman Debra T. , Hewitt Stephen M. , Moore Lee E. 
Published: September 2012

Abstract
Background: Cell-cycle proteins are important predictive markers in urothelial carcinoma but may also exhibit exposure-specific heterogeneity.
Methods: Tumor tissue from 491 bladder cancer cases enrolled in the Maine and Vermont component of the New England Bladder Cancer Study was assembled as tissue microarrays and examined for aberrant expression of p53, p63, p16, cyclin D1, Rb, and Ki-67. The association between expression and histopathology, demographics, and cigarette smoking was examined using χ2 tests, multivariable Poisson, and multinomial regression models.
Results: We found that overexpression of p53 and Ki-67 was associated with high-stage/grade tumors [relative risk (RR), 1.26; Ptrend = 0.003; and RR, 3.21; Ptrend &lt; 0.0001, respectively], whereas expression of p63 and p16 was decreased in high-stage/grade tumors (RR, 0.52; Ptrend &lt; 0.0001; and RR, 0.88; Ptrend = 0.04, respectively). No significant aberrations of cell-cycle proteins were identified using various smoking variables and multiple statistical models.
Conclusion: The results of this population-based study of histologically confirmed urothelial carcinomas show significant aberration of cell-cycle proteins p53, p63, p16, and Ki-67, but not Rb or cyclin D1. p53 showed the most significant heterogeneity with respect to tumor stage and grade, especially when stratified for different staining intensities using novel digital image analysis techniques. Our findings do not support that smoking modifies expression of cell-cycle proteins.
Impact: Our study shows significant heterogeneity in the expression of key cell-cycle proteins that are associated with disease progression in bladder cancer. Further studies may lead to the identification of biomarkers and their multiplexed interactions as useful prognostic and therapeutic targets. Cancer Epidemiol Biomarkers Prev; 21(9); 1555–64. ©2012 AACR.
Mammographic Screening and Breast Cancer Mortality: A Case–Control Study and Meta-analysis
Authors: Nickson Carolyn , Mason Kate E. , English Dallas R. , Kavanagh Anne M. 
Published: September 2012

Abstract
Background: Observational studies are necessary to assess the impact of population screening on breast cancer mortality. While some ecological studies have notably found little or no association, case–control studies consistently show strong inverse associations, but they are sometimes ignored, perhaps due to theoretical biases arising from the study design. We conducted a case–control study of breast cancer deaths in Western Australia to evaluate the effect of participation in the BreastScreen Australia program, paying particular attention to potential sources of bias, and undertook an updated meta-analysis of case–control studies.
Methods: Our study included 427 cases (women who died from breast cancer), each matched to up to 10 controls. We estimated the association between screening participation and breast cancer mortality, quantifying the effect of potential sources of bias on our findings, including selection bias, information bias, and confounding. We also conducted a meta-analysis of published case–control studies.
Results: The OR for participation in the Western Australian BreastScreen program in relation to death from breast cancer was 0.48 [95% confidence interval (CI), 0.38–0.59; P &lt; 0.001]. We were unable to identify biases that could negate this finding: sensitivity analyses generated ORs from 0.45 to 0.52. Our meta-analysis yielded an OR of 0.51 (95% CI, 0.46–0.55).
Conclusions: Our findings suggest an average 49% reduction in breast cancer mortality for women who are screened. In practice, theoretical biases have little effect on estimates from case–control studies.
Impact: Case–control studies, such as ours, provide robust and consistent evidence that screening benefits women who choose to be screened. Cancer Epidemiol Biomarkers Prev; 21(9); 1479–88. ©2012 AACR.