bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adenovirus E1B 55-Kilodalton Protein Is a p53-SUMO1 E3 Ligase That Represses p53 and Stimulates Its Nuclear Export through Interactions with Promyelocytic Leukemia Nuclear Bodies
Authors: Pennella Mario A. , Liu Yue , Woo Jennifer L. , Kim Chongwoo A. , Berk Arnold J. 
Published: September 2010

ABSTRACT

Oncogenic transformation by adenovirus E1A and E1B-55K requires E1B-55K inhibition of p53 activity to prevent E1A-induced apoptosis. During viral infection, E1B-55K and E4orf6 substitute for the substrate-binding subunits of the host cell cullin 5 class of ubiquitin ligases, resulting in p53 polyubiquitinylation and proteasomal degradation. Here we show that E1B-55K alone also functions as an E3 SUMO1-p53 ligase. Fluorescence microscopy studies showed that E1B-55K alone, in the absence of other viral proteins, causes p53 to colocalize with E1B-55K in promyelocytic leukemia (PML) nuclear bodies, nuclear domains with a high concentration of sumoylated proteins. Photobleaching experiments with live cells revealed that E1B-55K tethering of p53 in PML nuclear bodies decreases the
in vivo
nuclear mobility of p53 nearly 2 orders of magnitude. E1B-55K-induced p53 sumoylation contributes to maximal inhibition of p53 function since mutation of the major p53 sumoylation site decreases E1B-55K-induced p53 sumoylation, tethering in PML nuclear bodies, and E1B-55K inhibition of p53 activity. Mutation of the E1B-55K sumoylation site greatly inhibits E1B-55K association with PML nuclear bodies and the p53 nuclear export to cytoplasmic aggresomes observed in E1A-E1B-transformed cells. Purified E1B-55K and p53 form high-molecular-weight complexes potentially through the formation of a network of E1B-55K dimers bound to the N termini of p53 tetramers. In support of this model, a p53 mutation that prevents tetramer formation greatly reduces E1B-55K-induced tethering in PML nuclear bodies and p53 nuclear export. These data indicate that E1B-55K's association with PML nuclear bodies inactivates p53 by first sequestering it in PML nuclear bodies and then greatly facilitating its nuclear export.
Cell-Cell Spread of Human Immunodeficiency Virus Type 1 Overcomes Tetherin/BST-2-Mediated Restriction in T cells
Authors: Jolly Clare , Booth Nicola J. , Neil Stuart J. D. 
Published: September 2010

ABSTRACT

Direct cell-to-cell spread of human immunodeficiency virus type 1 (HIV-1) between T cells at the virological synapse (VS) is an efficient mechanism of viral dissemination. Tetherin (BST-2/CD317) is an interferon-induced, antiretroviral restriction factor that inhibits nascent cell-free particle release. The HIV-1 Vpu protein antagonizes tetherin activity; however, whether tetherin also restricts cell-cell spread is unclear. We performed quantitative cell-to-cell transfer analysis of wild-type (WT) or Vpu-defective HIV-1 in Jurkat and primary CD4
+
T cells, both of which express endogenous levels of tetherin. We found that Vpu-defective HIV-1 appeared to disseminate more efficiently by cell-to-cell contact between Jurkat cells under conditions where tetherin restricted cell-free virion release. In T cells infected with Vpu-defective HIV-1, tetherin was enriched at the VS, and VS formation was increased compared to the WT, correlating with an accumulation of virus envelope proteins on the cell surface. Increasing tetherin expression with type I interferon had only minor effects on cell-to-cell transmission. Furthermore, small interfering RNA (siRNA)-mediated depletion of tetherin decreased VS formation and cell-to-cell transmission of both Vpu-defective and WT HIV-1. Taken together, these data demonstrate that tetherin does not restrict VS-mediated T cell-to-T cell transfer of Vpu-defective HIV-1 and suggest that under some circumstances tetherin might promote cell-to-cell transfer, either by mediating the accumulation of virions on the cell surface or by regulating integrity of the VS. If so, inhibition of tetherin activity by Vpu may balance requirements for efficient cell-free virion production and cell-to-cell transfer of HIV-1 in the face of antiviral immune responses.
Induction of a Cross-Reactive CD8+T Cell Response following Foot-and-Mouth Disease Virus Vaccination
Authors: Guzman Efrain , Taylor Geraldine , Charleston Bryan , Ellis Shirley A. 
Published: September 2010

ABSTRACTFoot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. Current inactivated FMDV vaccines generate short-term, serotype-specific protection, mainly through neutralizing antibody. An improved understanding of the mechanisms of protective immunity would aid design of more effective vaccines. We have previously reported the presence of virus-specific CD8+T cells in FMDV-vaccinated and -infected cattle. In the current study, we aimed to identify CD8+T cell epitopes in FMDV recognized by cattle vaccinated with inactivated FMDV serotype O. Analysis of gamma interferon (IFN-γ)-producing CD8+T cells responding to stimulation with FMDV-derived peptides revealed one putative CD8+T cell epitope present within the structural protein P1D, comprising residues 795 to 803 of FMDV serotype O UKG/2001. The restricting major histocompatibility complex (MHC) class I allele was N*02201, expressed by the A31 haplotype. This epitope induced IFN-γ release, proliferation, and target cell killing by αβ CD8+T cells, but not CD4+T cells. A protein alignment of representative samples from each of the 7 FMDV serotypes showed that the putative epitope is highly conserved. CD8+T cells from FMDV serotype O-vaccinated A31+cattle recognized antigen-presenting cells (APCs) loaded with peptides derived from all 7 FMDV serotypes, suggesting that CD8+T cells recognizing the defined epitope are cross-reactive to equivalent peptides derived from all of the other FMDV serotypes.
A Double Mutation in Glycoprotein gB Compensates for Ineffective gD-Dependent Initiation of Herpes Simplex Virus Type 1 Infection
Authors: Uchida Hiroaki , Chan Janet , Goins William F. , Grandi Paola , Kumagai Izumi , Cohen Justus B. , Glorioso Joseph C. 
Published: September 2010

ABSTRACT
Herpes simplex virus (HSV) entry into cells is triggered by the binding of envelope glycoprotein D (gD) to a specific receptor, such as nectin-1 or herpesvirus entry mediator (HVEM), resulting in activation of the fusion effectors gB and gH and virus penetration. Here we report the identification of a hyperactive gB allele, D285N/A549T, selected by repeat passage of a gD mutant virus defective for nectin-1 binding through cells that express a gD-binding-impaired mutant nectin-1. The gB allele in a wild-type virus background enabled the use of other nectins as virus entry receptors. In addition, combination of the mutant allele with an epidermal growth factor receptor (EGFR)-retargeted gD gene yielded dramatically increased EGFR-specific virus entry compared to retargeted virus carrying wild-type gB. Entry of the gB mutant virus into nectin-1-bearing cells was markedly accelerated compared to that of wild-type virus, suggesting that the gB mutations affect a rate-limiting step in entry. Our observations indicate that ineffective gD activation can be complemented by hypersensitization of a downstream component of the entry cascade to gD signaling.
ATR and ATRIP Are Recruited to Herpes Simplex Virus Type 1 Replication Compartments Even though ATR Signaling Is Disabled
Authors: Mohni Kareem N. , Livingston Christine M. , Cortez David , Weller Sandra K. 
Published: September 2010

ABSTRACT
Although the herpes simplex virus type 1 (HSV-1) genome might be expected to induce a DNA damage response, the ATR kinase is not activated in infected cells. We previously proposed that spatial uncoupling of ATR from its interaction partner, ATRIP, could be the basis for inactivation of the ATR kinase in infected cells; however, we now show that ATR and ATRIP are in fact both recruited to HSV-1 replication compartments and can be coimmunoprecipitated from infected-cell lysates. ATRIP and replication protein A (RPA) are recruited to the earliest detectable prereplicative sites, stage II microfoci. In a normal cellular DNA damage response, ATR/ATRIP are recruited to stretches of RPA-coated single-stranded DNA in an RPA- and kinase-dependent manner, resulting in the phosphorylation of RPA by ATR in damage foci. In contrast, in HSV-1-infected cells, RPA is not phosphorylated, and endogenous phosphorylated RPA is excluded from stage II microfoci; in addition, the recruitment of ATR/ATRIP is independent of RPA and the kinase activity of ATR. Furthermore, we show that ATR/ATRIP play a beneficial role in viral gene expression and virus production. Although ICP0 has been shown to be important for partial inactivation of other cellular DNA repair pathways, we show that ICP0 is not responsible for the inactivation of ATR signaling and, furthermore, that neither ATR nor ATRIP is a target of ICP0 degradation. Thus, ATR and ATRIP may function outside the context of the canonical ATR damage signaling pathway during HSV-1 infection to participate in the viral life cycle.
Does constipation predict the quality of bowel preparation during colonoscopy?
Authors: Bloom Peter , Shustina Alexandra , Gaetano John N , Gualtieri Nicholas , Tievsky Dana , Robilotti James G 
Published: September 2010

BackgroundSuboptimal bowel preparation has several consequences, including reduced polyp detection rate and increased cost of colorectal cancer screening. The presence of constipation is thought to be a feature associated with poor bowel preparation.ObjectivesTo characterise the relationship between features of constipation and the quality of bowel preparation during colonoscopy.DesignPatients presenting for an outpatient colonoscopy were asked to complete a questionnaire which included demographics, type of bowel purgative and features of bowel movements (BMs)—derived from the ROME III criteria for diagnosis of chronic constipation.Patients101 patients from the community undergoing surveillance colonoscopy completed the study.InterventionsPatients underwent standard bowel preparation, completed a pre-endoscopy survey, followed by routine surveillance colonoscopy.Main outcome measurementsThe endoscopist rated the quality of bowel preparation using the previously validated Ottawa scoring scale. Statistical analysis was performed to characterise the relationship between the existence of chronic constipation and quality of bowel preparation.ResultsBM frequency of <1/day, 1/day, 2/day, or 3/day was inversely correlated with average total Ottawa score (range 5.93 to 4.00), p=0.028) as well as recto-sigmoid Ottawa score (range 1.8 to 1.0, p=0.006). Among women, there was a statistically significant (p=0.025) association between those who reported hard stools (Ottawa=6.3) and those who denied hard stools (4.5).ConclusionEliciting features of BMs before colonoscopy may predict those at risk for poor bowel preparations and increase cost effectiveness of colonoscopy.
Bypassing the selection rule in choosing controls for a case–control study
Authors: Palmer Keith T , Kim Miranda , Coggon David 
Published: September 2010

ObjectivesIt has been argued that in case–control studies, controls should be drawn from the base population that gives rise to the cases. In designing a study of occupational injury and risks arising from long-term illness and prescribed medication, we lacked data on subjects' occupation, without which employed cases (typically in manual occupations) would be compared with controls from the general population, including the unemployed and a higher proportion of white-collar professions. Collecting the missing data on occupation would be costly. We estimated the potential for bias if the selection rule were ignored.MethodsWe obtained published estimates of the frequencies of several exposures of interest (diabetes, mental health problems, asthma, coronary heart disease) in the general population, and of the relative risks of these diseases in unemployed versus employed individuals and in manual versus non-manual occupations. From these we computed the degree of over- or underestimation of exposure frequencies and exposure ORs if controls were selected from the general population.ResultsThe potential bias in the OR was estimated as likely to fall between an underestimation of 14% and an overestimation of 36.7% (95th centiles). In fewer than 6% of simulations did the error exceed 30%, and in none did it reach 50%.ConclusionsFor the purposes of this study, in which we were interested only in substantial increases in risk, the potential for selection bias was judged acceptable. The rule that controls should come from the same base population as cases can justifiably be broken, at least in some circumstances.
Can exposure to a terrestrial trunked radio (TETRA)-like signal cause symptoms? A randomised double-blind provocation study
Authors: Nieto-Hernandez Rosa , Williams Jonathan , Cleare Anthony J , Landau Sabine , Wessely Simon , Rubin G James 
Published: September 2010

ObjectivesConcerns have been raised about possible health effects from radiofrequency fields pulsing at around 16 Hz. A radio system used by UK police (TETRA) employs signals which pulse at 17.6 Hz. We tested whether exposure to a continuous wave signal at 385.25 MHz or a TETRA-like signal resulted in symptoms among users reporting sensitivity to TETRA compared to users not reporting sensitivity to TETRA.Methods60 sensitive and 60 non-sensitive users were exposed to three 50 min conditions: a signal with a 16 Hz component, a continuous wave condition and a sham condition. The mean radiated power for the 16 Hz and continuous wave conditions was 250 mW. The order of conditions was randomised and testing was conducted double-blind. Participants reported the severity of eight symptoms during and after each exposure, their mood state at the end of each exposure, and whether they could tell which sessions involved active signals. The study was registered in advance with the ISRCTN register.ResultsExposure to the continuous wave signal increased ratings of headache in all participants, fatigue in non-sensitive participants and difficulty concentrating in sensitive participants. Paradoxically, it reduced sensations of itching in sensitive participants. These effects were not observed in the condition with 16 Hz pulsing, except for those relating to concentration. Adjusting for multiple comparisons removed most significant effects, but not those relating to itch.ConclusionsThe results suggested that exposure to TETRA signals is not responsible for symptoms reported by some users, although exposure to a continuous wave signal may affect symptoms.Clinical trial numberISRCTN 73321766.
Brick1 Is an Essential Regulator of Actin Cytoskeleton Required for Embryonic Development and Cell Transformation
Authors: Escobar Beatriz , de Cárcer Guillermo , Fernández-Miranda Gonzalo , Cascón Alberto , Bravo-Cordero José J. , Montoya María C. , Robledo Mercedes , Cañamero Marta , Malumbres Marcos 
Published: September 2010

Abstract
Brick1 (Brk1) is the less-studied component of the Wave/Scar pathway involved in the branched nucleation of actin fibers. The clinical relevance of Brk1 is emphasized by correlative data showing that Von Hippel-Lindau (VHL) patients that also lose the BRK1 gene are protected against the development of tumors. This contrasts with recent evidence suggesting that the Wave complex may function as an invasion suppressor in epithelial cancers. Here, we show that the downregulation of Brk1 results in abnormal actin stress fiber formation and vinculin distribution and loss of Arp2/3 and Wave proteins at the cellular protrusions. Brk1 is required for cell proliferation and cell transformation by oncogenes. In addition, Brk1 downregulation results in defective directional migration and invasive growth in renal cell carcinoma cells as well as in other tumor cell types. Finally, genetic ablation of Brk1 results in dramatic defects in embryo compaction and development, suggesting an essential role for this protein in actin dynamics. Thus, genetic loss or inhibition of BRK1 is likely to be protective against tumor development due to proliferation and motility defects in affected cells. Cancer Res; 70(22); 9349–59. ©2010 AACR.
A New Paradigm for Aptamer Therapeutic AS1411 Action: Uptake by Macropinocytosis and Its Stimulation by a Nucleolin-Dependent Mechanism
Authors: Reyes-Reyes E. Merit , Teng Yun , Bates Paula J. 
Published: September 2010

Abstract
AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to novel targeted therapies. Previously, we proposed a model where cell surface nucleolin serves as the receptor for AS1411, leading to selective uptake in cancer cells. Here, we compare uptake of fluorophore-labeled AS1411 (FL-AS1411) in DU145 prostate cancer cells (sensitive to AS1411) and Hs27 nonmalignant skin fibroblasts (resistant to AS1411). Uptake of FL-AS1411 occurred by endocytosis in both cell types and was much more efficient than an inactive, nonquadruplex oligonucleotide. Unexpectedly, uptake of FL-AS1411 was lower in cancer cells compared with Hs27 cells. However, the mechanism of uptake was different, occurring by macropinocytosis in cancer cells, but by a nonmacropinocytic pathway in Hs27 cells. Additionally, treatment of various cancer cells with AS1411 caused hyperstimulation of macropinocytosis, provoking an increase in its own uptake, whereas no stimulation was observed for nonmalignant cells. Nucleolin was not required for initial FL-AS1411 uptake in DU145 cells but was necessary for induced macropinocytosis and FL-AS1411 uptake at later times. Our results are inconsistent with the previous mechanistic model but confirm that nucleolin plays a role in mediating AS1411 effects. The data suggest a new model for AS1411 action as well as a new role for nucleolin in stimulating macropinocytosis, a process with potential applications in drug delivery. Cancer Res; 70(21); 8617–29. ©2010 AACR.
A Different Approach to the History of Islam and Muslims in Europe: A North-Eastern Angle, or the Need to Reconsider the Research Field
Authors: Larsson Göran , Račius Egdūnas 
Published: September 2010

AbstractWhile the ever more strongly felt presence of Muslims in western Europe has already stimulated numerous scholars of various social sciences to embark upon research on issues related to that presence, it is apparent that just a few studies and introductory text books have so far dealt with the evolution of Muslim communities in other parts of Europe, especially in countries of central, eastern, and northern Europe. Without appreciation of and comprehensive research into the more than six-hundred-year-long Muslim presence in the eastern Baltic rim the picture of the development of Islam and Muslim-Christian relations in Europe remains incomplete and even distorted. Therefore, this article argues for the necessity of approaching the history of Islam and Muslims in Europe from a different and ultimately more encompassing angle by including the minorities of Muslim cultural background that reside in the countries of the European part of the former Soviet Union—the Baltic states and Belarus. Besides arguing that it is necessary to reconsider and expand the research field in order to develop more profound studies of Islam and Muslims in Europe, the article also outlines suggestions as to why the Muslim history in the eastern Baltic rim has been generally excluded from the history of Islam in Europe.
Public Religion and State Transformation: Zero-Sum Game or Fruitful Partnership?
Authors: Nagel Alexander-Kenneth 
Published: September 2010

AbstractModern nation states appear to be under siege: economic transactions and environmental pressures come along in global dimensions and along with transnational mass communication and religious communities call into question the paradigm of secular nationalism. While political scientists have supplied useful heuristics to examine the transformation of modern states under these conditions, they have widely disparaged the religious factor as a premodern atavism. Scholars of religious studies, on the other hand, have celebrated the 'new' publicity of religion, but established an overtly antagonistic concept of religion and the state. In this article I try to connect the two debates by arguing that the role of public religion for state transformation can be understood in institutionalist terms of public-private partnerships rather than as a zero-sum game.
Links between the Southern Annular Mode and the Atlantic Meridional Overturning Circulation in a Climate Model
Authors: Marini Camille , Frankignoul Claude , Mignot Juliette 
Published: September 2010

Abstract
The links between the atmospheric southern annular mode (SAM), the Southern Ocean, and the Atlantic meridional overturning circulation (AMOC) at interannual to multidecadal time scales are investigated in a 500-yr control integration of the L’Institut Pierre-Simon Laplace Coupled Model, version 4 (IPSL CM4) climate model. The Antarctic Circumpolar Current, as described by its transport through the Drake Passage, is well correlated with the SAM at the yearly time scale, reflecting that an intensification of the westerlies south of 45°S leads to its acceleration. Also in phase with a positive SAM, the global meridional overturning circulation is modified in the Southern Hemisphere, primarily reflecting a forced barotropic response. In the model, the AMOC and the SAM are linked at several time scales. An intensification of the AMOC lags a positive SAM by about 8 yr. This is due to a correlation between the SAM and the atmospheric circulation in the northern North Atlantic that reflects a symmetric ENSO influence on the two hemispheres, as well as an independent, delayed interhemispheric link driven by the SAM. Both effects lead to an intensification of the subpolar gyre and, by salinity advection, increased deep convection and a stronger AMOC. A slower oceanic link between the SAM and the AMOC is found at a multidecadal time scale. Salinity anomalies generated by the SAM enter the South Atlantic from the Drake Passage and, more importantly, the Indian Ocean; they propagate northward, eventually reaching the northern North Atlantic where, for a positive SAM, they decrease the vertical stratification and thus increase the AMOC.