bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structures of the Major Capsid Proteins of the Human Karolinska Institutet and Washington University Polyomaviruses
Authors: Neu Ursula , Wang Jianbo , Macejak Dennis , Garcea Robert L. , Stehle Thilo 
Published: May 2011

ABSTRACT
The Karolinska Institutet and Washington University polyomaviruses (KIPyV and WUPyV, respectively) are recently discovered human viruses that infect the respiratory tract. Although they have not yet been linked to disease, they are prevalent in populations worldwide, with initial infection occurring in early childhood. Polyomavirus capsids consist of 72 pentamers of the major capsid protein viral protein 1 (VP1), which determines antigenicity and receptor specificity. The WUPyV and KIPyV VP1 proteins are distant in evolution from VP1 proteins of known structure such as simian virus 40 or murine polyomavirus. We present here the crystal structures of unassembled recombinant WUPyV and KIPyV VP1 pentamers at resolutions of 2.9 and 2.55 Å, respectively. The WUPyV and KIPyV VP1 core structures fold into the same β-sandwich that is a hallmark of all polyomavirus VP1 proteins crystallized to date. However, differences in sequence translate into profoundly different surface loop structures in KIPyV and WUPyV VP1 proteins. Such loop structures have not been observed for other polyomaviruses, and they provide initial clues about the possible interactions of these viruses with cell surface receptors.
Inhibition of Human BK Polyomavirus Replication by Small Noncoding RNAs
Authors: Tikhanovich Irina , Liang Bo , Seoighe Cathal , Folk William R. , Nasheuer Heinz Peter 
Published: May 2011

ABSTRACT

Small noncoding RNAs regulate a variety of cellular processes, including genomic imprinting, chromatin remodeling, replication, transcription, and translation. Here, we report small replication-regulating RNAs (srRNAs) that specifically inhibit DNA replication of the human BK polyomavirus (BKV)
in vitro
and
in vivo
. srRNAs from FM3A murine mammary tumor cells were enriched by DNA replication assay-guided fractionation and hybridization to the BKV noncoding control region (NCCR) and synthesized as cDNAs. Selective mutagenesis of the cDNA sequences and their putative targets suggests that the inhibition of BKV DNA replication is mediated by srRNAs binding to the viral NCCR, hindering early steps in the initiation of DNA replication. Ectopic expression of srRNAs in human cells inhibited BKV DNA replication
in vivo
. Additional srRNAs were designed and synthesized that specifically inhibit simian virus 40 (SV40) DNA replication
in vitro
. These observations point to novel mechanisms for regulating DNA replication and suggest the design of synthetic agents for inhibiting replication of polyomaviruses and possibly other viruses.
Entry of Tiger Frog Virus (an Iridovirus) into HepG2 Cells via a pH-Dependent, Atypical, Caveola-Mediated Endocytosis Pathway
Authors: Guo Chang-Jun , Liu Dong , Wu Yan-Yan , Yang Xiao-Bo , Yang Li-Shi , Mi Shu , Huang Yu-Xin , Luo Yong-Wen , Jia Kun-Tong , Liu Zhao-Yu , Chen Wei-Jian , Weng Shao-Ping , Yu Xiao-Qiang , He Jian-Guo 
Published: May 2011

ABSTRACT

Tiger frog virus (TFV), in the genus
Ranavirus
of the family
Iridoviridae
, causes high mortality of cultured tiger frog tadpoles in China. To explore the cellular entry mechanism of TFV, HepG2 cells were treated with drugs that inhibit the main endocytic pathways. We observed that TFV entry was inhibited by NH
4
Cl, chloroquine, and bafilomycin, which can all elevate the pH of acidic organelles. In contrast, TFV entry was not influenced by chlorpromazine or overexpression of a dominant-negative form of Esp15, which inhibit the assembly of clathrin-coated pits. These results suggested that TFV entry was not associated with clathrin-mediated endocytosis, but was related to the pH of acidic organelles. Subsequently, we found that endocytosis of TFV was dependent on membrane cholesterol and was inhibited by the caveolin-1 scaffolding domain peptide. Dynamin and actin were also required for TFV entry. In addition, TFV virions colocalized with the cholera toxin subunit B, indicating that TFV enters as caveola-internalized cargo into the Golgi complex. Taken together, our results demonstrated that TFV entry occurs by caveola-mediated endocytosis with a pH-dependent step. This atypical caveola-mediated endocytosis is different from the clathrin-mediated endocytosis of frog virus 3 (FV3) by BHK cells, which has been recognized as a model for iridoviruses. Thus, our work may help further the understanding of the initial steps of iridovirus infection in lower vertebrates.
NRIP, a Novel Calmodulin Binding Protein, Activates Calcineurin To Dephosphorylate Human Papillomavirus E2 Protein
Authors: Chang Szu-Wei , Tsao Yeou-Ping , Lin Chia-Yi , Chen Show-Li 
Published: May 2011

ABSTRACT

Previously, we found a gene named nuclear receptor interaction protein (NRIP) (or DCAF6 or IQWD1). We demonstrate that NRIP is a novel binding protein for human papillomavirus 16 (HPV-16) E2 protein. HPV-16 E2 and NRIP can directly associate into a complex
in vivo
and
in vitro
, and the N-terminal domain of NRIP interacts with the transactivation domain of HPV-16 E2. Only full-length NRIP can stabilize E2 protein and induce HPV gene expression, and NRIP silenced by two designed small interfering RNAs (siRNAs) decreases E2 protein levels and E2-driven gene expression. We found that NRIP can directly bind with calmodulin in the presence of calcium through its IQ domain, resulting in decreased E2 ubiquitination and increased E2 protein stability. Complex formation between NRIP and calcium/calmodulin activates the phosphatase calcineurin to dephosphorylate E2 and increase E2 protein stability. We present evidences for E2 phosphorylation
in vivo
and show that NRIP acts as a scaffold to recruit E2 and calcium/calmodulin to prevent polyubiquitination and degradation of E2, enhancing E2 stability and E2-driven gene expression.
A survey of patients' attitudes to upper gastrointestinal endoscopy identifies the value of endoscopist–patient interactive factors
Authors: Hydes T , Yusuf A , Pearl DS , Trebble TM 
Published: May 2011

ObjectiveTo determine patients’ self-reported preferences and expectations for outpatient upper gastrointestinal (UGI) endoscopy, including patients’ priorities in obtaining a satisfactory healthcare experience, preprocedure anxiety and its causes, and preferred staff roles.DesignA composite, dedicated endoscopy questionnaire was used. This included demographic information, validated Likert scale anxiety-related questions and a 15-point ranking scale of aspects of care (1=most important to satisfaction; 15=least important).Setting and patientsUnselected patients attending for an elective UGI endoscopy at two separate units were surveyed on randomly identified days.ResultsA total of 202 out of 254 patients agreed to participate (79.5%). The values identified as most important to patients included technical skill (2.8) and personal manner of the endoscopist (4.9) and the nurses and support staff (5.8), control of discomfort (5.6) and adequacy of the preprocedure explanation (5.8). The factors considered least important included noise levels (12.5), privacy (10.7) and cleanliness (8.7). Moderate to severe anxiety was recorded in half of the patient cohort, predominantly due to anticipation of pain or the results of the procedure. Most patients preferred the endoscopist to discuss the findings of the endoscopy but expressed no preferences regarding the preprocedure explanation.ConclusionPatients undergoing UGI endoscopy appear to highly prioritise aspects of care relating to interaction with the endoscopist and the procedure itself. Environmental factors are considered to have much less value. These findings may assist in service redesign around patient-centred care and the development of patient satisfaction surveys in endoscopy.
Impacts of permafrost degradation on a road embankment at Umiujaq in Nunavik (Quebec), Canada
Authors: Fortier Richard , LeBlanc Anne-Marie , Yu Wenbing 
Published: May 2011

Differential subsidence of as much as 0.85 m is affecting the access road to Umiujaq Airport in Nunavik (Quebec), Canada, located in the discontinuous permafrost zone. A geotechnical and geophysical investigation including piezocone test, ground-penetrating radar profiling, electrical resistivity tomography, and numerical modeling of the thermal regime of the road embankment and subgrade is presented to characterize the ground stratigraphy and permafrost conditions and to assess the exact causes and effects of permafrost degradation on the road embankment. The subsidence is due to thaw consolidation taking place in a layer of ice-rich silt underneath a superficial sand layer. While the seasonal freeze–thaw cycles were initially restricted to the sand layer, the thawing front has now reached the thaw-unstable ice-rich silt layer. According to our numerical modeling, the increase in air temperature recently observed in Nunavik cannot be the sole cause of the observed subsidence affecting this engineering structure. The thick embankment also acts as a snow fence favoring the accumulation of snow on the embankment shoulders. The permafrost degradation is also due to the thermal insulation of the snow cover reducing heat loss in the embankment shoulders and toes.
Sex Hormone Concentrations and the Risk of Breast Cancer Recurrence in Postmenopausal Women without Hot Flashes
Authors: Emond Jennifer A. , Patterson Ruth E. , Natarajan Loki , Laughlin Gail A. , Gold Ellen B. , Pierce John P. 
Published: May 2011

Abstract
Background: We examined if the reduced risk of breast cancer events seen among women without baseline hot flash symptoms in the Women's Healthy Eating and Living (WHEL) dietary intervention trial was related to changes in sex hormone concentrations.
Methods: Baseline and year one concentrations of total and bioavailable estradiol, and testosterone and sex hormone-binding globulin (SHBG) were compared by intervention arm among 447 postmenopausal women without hot flashes. Cox proportional hazard models tested interaction terms between study arm and baseline hormone concentrations adjusted for study site, antiestrogen use, positive nodes, tumor size, oophorectomy status, and hormone replacement therapy use.
Results: Sex hormone concentrations did not differ by study arm at baseline nor at year one. Twenty-two (9.8%) events occurred in the intervention arm versus 42 (18.9%) in the comparison arm (P = 0.009). Baseline bioavailable testosterone was significantly, positively associated with additional events (HR 1.69, 95% CI: 1.00–2.84; P = 0.049). There were significant interactions between the intervention and total (P = 0.015), and bioavailable (P = 0.050) testosterone: the intervention was more protective among participants with higher baseline total (HR 0.3, 95% CI: 0.2–0.7) or bioavailable (HR 0.4, 95% CI: 0.2–0.7) testosterone than for participants with lower baseline total (HR 0.8, 95% CI: 0.4–1.5) or bioavailable (HR 0.8, 95% CI: 0.4–1.5) testosterone. No significant effects were seen for estradiol or SHBG.
Conclusions: The WHEL dietary intervention may have modified other risk factors of recurrence correlated with testosterone.
Impact: Sex hormones should be considered as part of a larger biological system related to the risk of breast cancer recurrence. Cancer Epidemiol Biomarkers Prev; 20(5); 939–45. ©2011 AACR.
Inhibitor of Differentiation-1 as a Novel Prognostic Factor in NSCLC Patients with Adenocarcinoma Histology and Its Potential Contribution to Therapy Resistance
Authors: Ponz-Sarvisé Mariano , Nguewa Paul A. , Pajares María J. , Agorreta Jackeline , Lozano María D. , Redrado Miriam , Pio Ruben , Behrens Carmen , Wistuba Ignacio I. , García-Franco Carlos E. , García-Foncillas Jesús , Montuenga Luis M. , Calvo Alfonso , Gil-Bazo Ignacio 
Published: May 2011

Abstract
Purpose: High inhibitor of differentiation-1 (Id1) levels have been found in some tumor types. We aimed to study Id1 levels and their prognostic impact in a large series of stages I to IV non-small cell lung cancer (NSCLC) patients. Experiments in cell lines and cells derived from malignant pleural effusions (MPE) were also carried out.
Experimental Design: A total of 346 NSCLC samples (three different cohorts), including 65 matched nonmalignant tissues, were evaluated for Id1 expression by using immunohistochemistry. Additional data from a fourth cohort including 111 patients were obtained for Id1 mRNA expression analysis by using publicly available microarrays. In vitro proliferation assays were conducted to characterize the impact of Id1 on growth and treatment sensitivity.
Results: Significantly higher Id1 protein levels were found in tumors compared with normal tissues (P &lt; 0.001) and in squamous carcinomas compared with adenocarcinomas (P &lt; 0.001). In radically treated stages I to III patients and stage IV patients treated with chemotherapy, higher Id1 levels were associated with a shorter disease-free survival and overall survival in adenocarcinoma patients in a log-rank test. A Cox model confirmed the independent prognostic value of Id1 levels for both stages I to III and stage IV patients. In silico analysis confirmed a correlation between higher Id1 mRNA levels and poor prognosis for adenocarcinoma subjects. In vitro Id1 silencing in radio/chemotherapy-resistant adenocarcinoma cells from MPEs restored sensitivity to both therapies.
Conclusions: In our series, Id1 levels showed an independent prognostic value in patients with adenocarcinoma, regardless of the stage. Id1 silencing may sensitize adenocarcinoma cells to radiotherapy and chemotherapy. Clin Cancer Res; 17(12); 4155–66. ©2011 AACR.
von Willebrand factor abnormalities in aortic valve stenosis: Pathophysiology and impact on bleeding
Authors: Sponga Sandro , Pontara Elena , Cattini Maria Grazia , Basso Cristina , Thiene Gaetano , Cella Giuseppe , Daidone Viviana , Gerosa Gino , Pagnan Antonio , Casonato Alessandra 
Published: May 2011

SummaryAcquired von Willebrand syndrome (AVWS) may complicate severe aortic valve stenosis, due to a reduction in the haemostatically more efficient large von Willebrand factor (VWF) multimers. This study was designed to analyse the relevance of VWF abnormalities and haemorrhagic diathesis in severe aortic valve stenosis. Forty-one consecutive patients undergoing valve replacement were investigated: seven had minor bleeding symptoms in their recent history; 10 (24.3%) had a reduced VWF collagen binding (VWF:CB) to VWF antigen ratio, and 33 (80.5%) had a decrease in large VWF multimers. The shortage of large multimers was not associated with any accumulation of small VWF multimers (apparently ruling out any increased VWF proteolysis), nor was there any increase in VWF propeptide, which excludes a shorter VWF survival. The risk of developing VWF abnormalities was higher in patients with rheumatic valve disease than in degenerative cases (p=0.025) and in valves with <50% of residual endothelial cells (p=0.004). Bleeders differed from non-bleeders in that they had a higher mean transvalvular gradient and a more marked decrease in large VWF multimers. VWF abnormalities did not exacerbate peri-operative blood loss, however – a finding consistent with the full correction of these VWF abnormalities, seen already on the first postoperative day and persisting for up to six months after surgery. According to the data obtained in our cohort of patients VWF abnormalities are common in severe aortic stenosis, particularly in cases of rheumatic valve disease, but loss of the largest multimers does not seem to cause clinical bleeding in most patients.
Observing Climate at High Elevations Using United States Climate Reference Network Approaches
Authors: Palecki Michael A. , Groisman Pavel Ya. 
Published: May 2011

AbstractThe U.S. Climate Reference Network (USCRN) was deployed between 2001 and 2008 for the purpose of yielding high-quality and temporally stable in situ climate observations in pristine environments over the twenty-first century. Given this mission, USCRN stations are engineered to operate largely autonomously with great reliability and accuracy. A triplicate approach is used to provide redundant measurements of temperature and precipitation at each location, allowing for observations at a specific time to be compared for quality control. This approach has proven to be robust in the most extreme environments, from extreme cold (−49°C) to extreme heat (+52°C), in areas of heavy precipitation (4700 mm yr−1), and in locations impacted by strong winds, freezing rain, and other hazards. In addition to a number of stations enduring extreme winter environments in Alaska and the northern United States, seven of the USCRN stations are located at elevations over 2000 m, including stations on Mauna Loa, Hawaii (3407 m) and on Niwot Ridge above Boulder, Colorado (2996 m). The USCRN temperature instruments and radiation shield have also been installed and run successfully at a station on the Quelccaya Ice Cap in Peru (5670 m). This paper reviews the performance of the USCRN station network during its brief lifetime and the potential utility of its triplicate temperature instrument configuration for measuring climate change at elevation.
Graft Uptake Rates with Isoamyl‐2‐Cyanoacrylate in Myringoplasty Procedures
Authors: Deenadayal Dasari Samuel , Neeli Ajay Kumar , Patel Saif Hameed 
Published: May 2011

ObjectiveTo assess graft uptake rates with the use of cyanoacrylate adhesives in myringoplasty procedures.Study DesignCase series with chart review.SettingTertiary care center.Subjects and MethodsFive hundred forty‐two patients selected with safe central perforations were divided into 4 groups based on perforation size and each divided into 2 subgroups depending on the presence or absence of preexisting pathology on the remnant tympanic membrane. Myringoplasty without ossicular reconstruction was done postaurally or by transcanal approach, with inlay graft placed and adhesive applied. Ear pack was removed on the seventh postoperative day. Graft uptake rates, graft uptake time (neotympanum intact and mobile), and postoperative sequelae were noted.ResultsGraft uptake was about 99% at 3 months postsurgery. Residual perforation was seen in 2 patients in group 2 and 1 in group 4 and thinned‐out tympanum in 1 patient in group 4. Mean uptake time was 21 days. Neotympanum mobility was sluggish in 9 cases postoperatively in group 4 and in 2 cases in group 3. Patients with successful (neotympanum intact and mobile) graft uptake showed significant improvement. Postoperative inflammatory signs in the external auditory canal were seen in 3 cases.ConclusionCyanoacrylate use in myringoplasty obtains graft uptake rates of 99% compared with most studies, which report 80% to 90%. This also allows removal of the pack by the seventh day, allowing close follow‐up of the graft and less patient discomfort. Importantly, it has not interfered with the formation of the neotympanum or compromised hearing improvement.
Late onset lupus nephritis in Chinese patients: Classified by the 2003 International Society of Nephrology and Renal Pathology Society system
Authors: Xu Y-X , Tan Y , Yu F , Zhao M-H 
Published: May 2011

Aim: The aim of this study was to assess clinicopathological characteristics and outcomes of a cohort of Chinese patients with late onset lupus nephritis. Methods: Clinical, pathological and outcome data for patients with late onset lupus nephritis (onset at age ≥50 years) and early onset lupus nephritis (onset at age ≤40 years) were retrospectively analyzed and compared. Results: Among 271 patients with renal biopsy-proven lupus nephritis, 30 were identified as having late onset lupus nephritis and 241 were identified as having early onset lupus nephritis. Lower female predominance was observed in the late onset patients ( p = 0.06). The interval between presentation of lupus nephritis and diagnosis was significantly longer in the late onset group than in the early onset group ( p = 0.003). In comparison with early onset group, patients in the late onset group had significantly lower scores for endocapillary hypercellularity ( p = 0.041), subendothelial hyaline deposits ( p = 0.022) and glomerular leukocyte infiltration ( p = 0.032), but had significantly higher scores for tubular atrophy ( p = 0.037) and interstitial fibrosis ( p = 0.018). Regarding long-term survival and renal outcome, there was no significant difference between the two groups, although it seemed that the early onset group had a poorer renal outcome ( p = 0.077, hazard ratio (HR) = 3.909, 95% CI: 0.862–17.726). Conclusions: Patients with late onset lupus nephritis were usually diagnosed later; they had milder active lesions and more severe chronic lesions in renal pathology. However, the renal outcome was similar between late and early onset patients.
Toll-like receptor 7 (TLR7)–driven accumulation of a novel CD11c+ B-cell population is important for the development of autoimmunity
Authors: Rubtsov Anatoly V. , Rubtsova Kira , Fischer Aryeh , Meehan Richard T. , Gillis Joann Z. , Kappler John W. , Marrack Philippa 
Published: May 2011

Abstract
Females are more susceptible than males to many autoimmune diseases. The processes causing this phenomenon are incompletely understood. Here, we demonstrate that aged female mice acquire a previously uncharacterized population of B cells that we call age-associated B cells (ABCs) and that these cells express integrin αX chain (CD11c). This unexpected population also appears in young lupus-prone mice. On stimulation, CD11c+ B cells, both from autoimmune-prone and healthy strains of mice, secrete autoantibodies, and depletion of these cells in vivo leads to reduction of autoreactive antibodies, suggesting that the cells might have a direct role in the development of autoimmunity. We have explored factors that contribute to appearance of ABCs and demonstrated that signaling through Toll-like receptor 7 is crucial for development of this B cell population. We were able to detect a similar population of B cells in the peripheral blood of some elderly women with autoimmune disease, suggesting that there may be parallels between the creation of ABC-like cells between mice and humans.