bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epstein-Barr Virus Nuclear Antigen 1 Interacts with Nm23-H1 in Lymphoblastoid Cell Lines and Inhibits Its Ability To Suppress Cell Migration
Authors: Murakami Masanao , Lan Ke , Subramanian Chitra , Robertson Erle S. 
Published: January 2005

ABSTRACT
Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) is expressed in the majority of latency programs in EBV-infected cells and is critical for the maintenance of EBV episomes in the infected cells. EBNA1 is also known to be involved in transcriptional activation and regulates expression of the EBV latent genes, including the EBNAs and LMP1. Thus, EBNA1 is a multifunctional protein with critical functions required for the persistence of the viral genome over successive generations, producing new daughter cells from the infected cell. We identify EBNA1 here as an interacting EBNA with the known suppressor of metastasis and cell migration, Nm23-H1. Nm23-H1 inhibits cell migration when expressed in cancer cells. We show that EBNA1 associates with Nm23-H1 in EBV-infected cells in vitro, as well as in lymphoblastoid cell lines (LCLs). Nm23-H1 predominantly localizes to the cytoplasm in BJAB and 293T cells; however, upon expression of EBNA1, Nm23-H1 is translocated to the nucleus in similar compartments to EBNA1, suggesting a potential functional role that is linked to EBNA1. Convincingly, in EBV-transformed LCLs Nm23-H1 is localized predominantly to the nucleus and colocalizes to similar compartment as EBNA1. Further, we tested the effects of EBNA1 on Nm23-H1-mediated suppression of cell migration and showed that EBNA1 rescues the suppression of cell migration mediated by Nm23-H1. These in vitro studies suggest that EBNA1 plays a critical role in regulating the activities of Nm23-H1, including cell migration, through a mechanism which involves direct interaction of this major regulator in EBV-infected cells.
Rodent Cells Support Key Functions of the Human Immunodeficiency Virus Type 1 Pathogenicity Factor Nef
Authors: Keppler Oliver T. , Allespach Ina , Schüller Lismarie , Fenard David , Greene Warner C. , Fackler Oliver T. 
Published: January 2005

ABSTRACT

After infection with human immunodeficiency virus (HIV), progression toward immunodeficiency is governed by a complex interplay of viral and host determinants. The viral accessory protein Nef is a key factor for the development of AIDS. Strains of HIV and simian immunodeficiency virus that lack functional
nef
genes either do not induce AIDS or do so only after a significant delay. The validity of a transgenic-small-animal model for de novo infection by HIV will depend on its ability to recapitulate the actions of critical factors of viral pathogenicity, such as Nef. We assessed the ability of rat, mouse, and hamster cells to support key effector functions of Nef. In cell lines from rodents, the subcellular distribution of wild-type HIV type 1 strain SF2 Nef and mutants was comparable to that in human cells. Nef downregulated human CD4 from the cell surface, was associated with p21-activated kinase activity, and enhanced the infectivity of HIV-1 virions. Importantly, these Nef-induced effects, as well as the downregulation of rat CD4 and major histocompatibility complex class I molecules, could also be demonstrated in primary T lymphocytes and macrophages from human CD4-transgenic rats. Thus, HIV-1 Nef exerts key functions in rodent cells. In line with our ongoing efforts to establish a transgenic-rat model of HIV disease, these results indicate that important aspects of viral pathogenesis could be addressed in a transgenic-rodent model permissive for de novo infection and that such a model would be valuable for evaluating the function of Nef in vivo.
Regulation of Expression of the Epstein-Barr Virus BamHI-A Rightward Transcripts
Authors: Chen Honglin , Huang Jian , Wu Frederick Y. , Liao Gangling , Hutt-Fletcher Lindsey , Hayward S. Diane 
Published: January 2005

ABSTRACT
The Epstein-Barr virus (EBV) BamHI-A rightward transcripts, or BARTs, are a family of mRNAs expressed in all EBV latency programs, including EBV-infected B cells in healthy carriers. Despite their ubiquitous expression, the regulation and biological function of BARTs are still unclear. In this study, the BART 5′ termini were characterized by using a procedure that selects capped, full-length mRNAs. Two TATA-less promoter regions, designated P1 and P2, were mapped. P1 had relatively high basal activity in both epithelial and B cells, whereas P2 exhibited higher activity in epithelial cells. Upon EBV infection of B cells, transcription from P1 was detected soon after infection, while expression from P2 was delayed. Promoter-reporter assays in transiently transfected cells revealed that P1 and P2 were differentially regulated. Interferon regulatory factor 7 (IRF7) and IRF5 negatively regulated P1 activity. c-Myc and C/EBP family members positively regulated P2. Regulation of P2 by C/EBPs was characterized by electrophoretic mobility shift assay, chromatin immunoprecipitation, and reporter assays. More-abundant BART expression in epithelial cells correlated with the relative expression of positive and negative regulators in these cells.
Semen-Specific Genetic Characteristics of Human Immunodeficiency Virus Type 1
env
Authors: Pillai Satish K. , Good Benjamin , Pond Sergei Kosakovsky , Wong Joseph K. , Strain Matt C. , Richman Douglas D. , Smith Davey M. 
Published: January 2005

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) in the male genital tract may comprise virus produced locally in addition to virus transported from the circulation. Virus produced in the male genital tract may be genetically distinct, due to tissue-specific cellular characteristics and immunological pressures. HIV-1
env
sequences derived from paired blood and semen samples from the Los Alamos HIV Sequence Database were analyzed to ascertain a male genital tract-specific viral signature. Machine learning algorithms could predict seminal tropism based on
env
sequences with accuracies exceeding 90%, suggesting that a strong genetic signature does exist for virus replicating in the male genital tract. Additionally, semen-derived viral populations exhibited constrained diversity (
P
< 0.05), decreased levels of positive selection (
P
< 0.025), decreased CXCR4 coreceptor utilization, and altered glycosylation patterns. Our analysis suggests that the male genital tract represents a distinct selective environment that contributes to the apparent genetic bottlenecks associated with the sexual transmission of HIV-1.
Differential Induction of Antiviral Effects against West Nile Virus in Primary Mouse Macrophages Derived from Flavivirus-Susceptible and Congenic Resistant Mice by Alpha/Beta Interferon and Poly(I-C)
Authors: Pantelic Ljiljana , Sivakumaran Haran , Urosevic Nadezda 
Published: January 2005

ABSTRACT
A cell model of primary macrophages isolated from the peritoneal cavity of flavivirus-susceptible and congenic resistant mice has been used to study the extent and kinetics of antiviral effects against West Nile virus upon priming with alpha/beta interferon (IFN-α/β) or poly(I-C) (pIC). The pattern of flavivirus resistance expressed after priming of cells in this model was in good agreement with the pattern of flavivirus resistance described in the brains of the corresponding mouse strains. While priming with either IFN-α/β or pIC completely blocked flavivirus replication in macrophages from resistant mice, it only transiently reduced flavivirus replication in macrophages from susceptible mice. It was only the combined pretreatment with IFN-α/β and pIC that elicited strong antiviral responses that completely prevented flavivirus replication in macrophages from susceptible mice. Primary macrophages isolated from the blood of healthy human donors expressed a similar need for double-stranded RNA (dsRNA) cofactor in developing efficient antiviral responses against West Nile virus. These findings reveal that the inefficient IFN-α/β-induced antiviral effects against flaviviruses in cells from susceptible hosts could be successfully complemented by an external dsRNA factor leading to the complete eradication of the virus. This treatment appears to compensate for the lack of an inborn resistance mechanism in cells from the susceptible host. Furthermore, it may also provide useful clues for the prevention and treatment of flavivirus infections.
Evidence for Heterogeneous Selective Pressures in the Evolution of the
env
Gene in Different Human Immunodeficiency Virus Type 1 Subtypes
Authors: Travers Simon A. A. , O'Connell Mary J. , McCormack Grace P. , McInerney James O. 
Published: January 2005

ABSTRACT

Recent studies have demonstrated the emergence of human immunodeficiency virus type 1 (HIV-1) subtypes with various levels of fitness. Using heterogeneous maximum-likelihood models of adaptive evolution implemented in the PAML software package, with
env
sequences representing each HIV-1 group M subtype, we examined the various intersubtype selective pressures operating across the
env
gene. We found heterogeneity of evolutionary mechanisms between the different subtypes with a category of amino acid sites observed that had undergone positive selection for subtypes C, F1, and G, while these sites had undergone purifying selection in all other subtypes. Also, amino acid sites within subtypes A and K that had undergone purifying selection were observed, while these sites had undergone positive selection in all other subtypes. The presence of such sites indicates heterogeneity of selective pressures within HIV-1 group M subtype evolution that may account for the various levels of fitness of the subtypes.
Atypical Fusion Peptide of Nelson Bay Virus Fusion-Associated Small Transmembrane Protein
Authors: Cheng LiTing T. , Plemper Richard K. , Compans Richard W. 
Published: January 2005

ABSTRACT
A 10-kDa nonstructural transmembrane protein (p10) encoded by a reovirus, Nelson Bay virus, has been shown to induce syncytium formation (34). Sequence analysis and structural studies identified p10 as a type I membrane protein with a central transmembrane domain, a cytoplasmic basic region, and an N-terminal hydrophobic domain (HD) that was hypothesized to function as a fusion peptide. We performed mutational analysis on this slightly hydrophobic motif to identify possible structural requirements for fusion activity. Bulky aliphatic residues were found to be essential for optimal fusion, and an aromatic or highly hydrophobic side chain was found to be required at position 12. The requirement for hydrophilic residues within the HD was also examined: substitution of 10-Ser or 14-Ser with hydrophobic residues was found to reduce cell surface expression of p10 and delayed the onset of syncytium formation. Nonconservative substitutions of charged residues in the HD did not have an effect on fusion activity. Taken together, our results suggest that the HD is involved in both syncytium formation and in determining p10 transport and surface expression.
Identification of Two Neutralizing Regions on the Severe Acute Respiratory Syndrome Coronavirus Spike Glycoprotein Produced from the Mammalian Expression System
Authors: Wang Shixia , Chou Te-hui W. , Sakhatskyy Pavlo V. , Huang Song , Lawrence John M. , Cao Hong , Huang Xiaoyun , Lu Shan 
Published: January 2005

ABSTRACT
The Spike (S) protein of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) plays important roles in viral pathogenesis and potentially in the development of an effective vaccine against this virulent infectious disease. In this study, the codon-optimized S gene of SARS-CoV was synthesized to construct DNA vaccine plasmids expressing either the full-length or segments of the S protein. High titer S-specific immunoglobulin G antibody responses were elicited in rabbits immunized with DNA against various segments of the S protein. Two neutralizing domains were identified on the S protein, one at the N terminus (Ser12-Thr535) and the other near the C terminus (Arg797-Ile1192).
Enhanced Cytotoxicity without Internuclear Spread of Adenovirus upon Cell Fusion by Measles Virus Glycoproteins
Authors: Horn German P. , Vongpunsawad Sompong , Kornmann Evelyn , Fritz Barbara , Dittmer Dirk P. , Cattaneo Roberto , Dobbelstein Matthias 
Published: January 2005

ABSTRACT
The efficiency of viruses in cancer therapy is enhanced by proteins that mediate the fusion of infected cells with their neighbors. It was reported that replication-competent adenovirus particles can spread between nuclei within fusion-generated syncytia. To assess this conjecture, we generated fusogenic adenoviruses that express a balanced ratio of the F and H glycoproteins of measles virus. The viruses displayed enhanced cytotoxicity but largely unchanged replication efficiencies compared to a nonfusogenic virus. Most notably, the virus genomes did not spread through fusion-generated multinuclear cells. Hence, adenovirus replication in syncytia remains largely restricted to initially transduced nuclei.
Anti-CXCR4 Monoclonal Antibodies Recognizing Overlapping Epitopes Differ Significantly in Their Ability To Inhibit Entry of Human Immunodeficiency Virus Type 1
Authors: Carnec Xavier , Quan Lan , Olson William C. , Hazan Uriel , Dragic Tatjana 
Published: January 2005

ABSTRACT
CXCR4 is one of two physiologically relevant human immunodeficiency type 1 (HIV-1) entry coreceptors. Studies of CXCR4 mutants have not clearly identified the determinants of coreceptor function and specificity. We therefore used a panel of monoclonal antibodies to further elucidate CXCR4 expression, structure, and function. Our findings show the existence of conformational subpopulations of CXCR4 that are in equilibrium on the cell surface but are not cell type specific as previously reported. HIV-1 X4 isolates can interact with multiple CXCR4 conformations in order to gain entry into target cells.
Conjugating Motion
Authors: Weissert Thomas 
Published: January 2005

AbstractOur conception of time changed from the lofty absolute coordinate of the classical paradigm to merely a connection between local reference frames, thanks to the Special Theory of Relativity, a connection that depends on knowing the relative velocity between frames, and that entails knowing local velocities. We measure local velocities using a clock that cannot give us precise time because knowing time depends solely on knowing the process that we use to generate time. In the case of both macroscopic and microscopic clocks, an intrinsic uncertainty blocks us from knowing both the dynamic and static states of the variables involved. By focusing on the conceptual process that we use to describe physical systems, we can approach a common epistemology of both microscopic and macroscopic dynamical systems. We find that both systems of description require that we inser t time implicitly into the formalism to account for the conservation of identity through our own psychological experience of time. Although we cannot define exactly the nature of the conserved identity, we can describe its evolution with pairs of conjugate variables, one tracking the static state and one the dynamic state. Uncertainty extends from our conceiving system into our descriptive theories. An epistemology that emphasizes the balance between the conjugate variables as they serve to describe the evolution of the identity provides a common ground on which to discuss both the Heisenberg uncertainty principle of quantum mechanics and the bounded randomness of a deterministic macroscopic system. We have seen time go from a global to a local phenomenon, and perhaps now we must allow time to become an epiphenomenon even at the local level, one that we ourselves insert to account for the continuity of our own conscious experience.
Memory of Futures
Authors: Adam Barbara 
Published: January 2005

AbstractWe think of memories as being focused on the past. However, our ability to move freely in the temporal realm of past, present and future is far more complex and sophisticated than commonsense would suggest. In this paper I am concerned with our capacity to produce and extend ourselves into the far future, for example through nuclear power or the genetic modification of food, on the one hand, and our inability to know the potential, diverse and multiple outcomes of this technologically constituted futurity, on the other. I focus on this discrepancy in order to explore what conceptual tools are available to us to take account of long-term futures produced by the industrial way of life. And I identify some historical approaches to the future on the assumption that the past may well hold vital clues for today's dilemma, hence my proposal to engage in 'memory of futures'. I conclude by considering the potential of 'memory aids for the future' as a means to better encompass in contemporary concerns the long-term futures of our making.
Memory, Consciousness, and Time in Nabokov's Lolita
Authors: Hasty Olga 
Published: January 2005

AbstractIn his "Confession of a White Widowed Male," Humbert Humbert, the fictional narrator of Nabokov's Lolita, writes: "I am not concerned with so-called 'sex' at all." In the context of a narrative that centers on his pedophilia, it is difficult to take this assertion seriously. Yet if we do, we come to appreciate that Humbert's sexuality is emblematic of a distinctly modernist response to the perennial question of how to counter temporal passage and the inevitable loss attendant on it. Nabokov's configuration of memory, consciousness, and time in Lolita shows how passage itself might be engaged in the creative enterprise of resisting loss.
Evaluation of Interregional Transport Using the MM5–SCIPUFF System
Authors: Deng Aijun , Seaman Nelson L. , Hunter Glenn K. , Stauffer David R. 
Published: January 2005

Abstract
Improved understanding of transport issues and source–receptor relationships on the interregional scale is dependent on reducing the uncertainties in the ability to define complex three-dimensional wind fields evolving in time. The numerical models used for this purpose have been upgraded substantially in recent years by introducing finer grid resolution, better representation of subgrid-scale physics, and practical four-dimensional data assimilation (FDDA) techniques that reduce the accumulation of errors over time. The impact of these improvements for interregional transport is investigated in this paper using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research Mesoscale Model (MM5) and the Second-Order Closure Integrated Puff (SCIPUFF) dispersion model to simulate the 1983 Cross-Appalachian Tracer Experiment (CAPTEX-83) episode 1 of 18–19 September 1983. Combining MM5 and SCIPUFF makes it possible to verify predicted tracer concentrations against observed surface concentrations collected during the CAPTEX-83 study. Conclusions from this study are as follows. 1) Not surprisingly, a baseline model configuration reflecting typical capabilities of the late 1980s (70-km horizontal grid, 15 vertical layers, older subgrid physics, and no FDDA) produced large meteorological errors that severely degraded the accuracy of the surface tracer concentrations predicted by SCIPUFF. 2) Improving the horizontal and vertical resolution of the MM5 to 12 km (typical for current operational model) and 32 layers led to some improvements in the statistical skill, but the further addition of more advanced physics produced much greater reductions of simulation errors. 3) The use of FDDA, along with 12-km resolution and improved physics, produced the overall best performance. 4) Further reduction of the horizontal grid size to 4 km had a detrimental effect on meteorological and plume-dispersion solutions in this case because of misrepresentation of convection associated with a cold front by the MM5's explicit moist physics.
The Dispersion Relation for Planetary Waves in the Presence of Mean Flow and Topography. Part I: Analytical Theory and One-Dimensional Examples
Authors: Killworth Peter D. , Blundell Jeffrey R. 
Published: January 2005

Abstract
An eigenvalue problem for the dispersion relation for planetary waves in the presence of mean flow and bottom topographic gradients is derived, under the Wentzel–Kramers–Brillouin–Jeffreys (WKBJ) assumption, for frequencies that are low when compared with the inertial frequency. Examples are given for the World Ocean that show a rich variety of behavior, including no frequency (or latitudinal) cutoff, solutions trapped at certain depths, coalescence of waves, and a lack of dispersion for most short waves.
Isopycnal Averaging at Constant Height. Part I: The Formulation and a Case Study
Authors: Nurser A. J. George , Lee Mei-Man 
Published: January 2005

Abstract
Simple Eulerian averaging of velocities, density, and tracers at constant position is the most natural way of averaging. However, Eulerian averaging gives incorrect watermass distributions and properties as well as spurious diabatic circulations such as the Deacon cell. Instead of averaging at constant height, averaging along isopycnals removes such fictitious mixing and diabatic circulations. Such isopycnal averaging is normally performed at constant latitude, that is, averaging along isopynals as they heave up and down. As a result, height information is lost and the sea surface becomes much warmer (or lighter) than with simple Eulerian averaging. In fact, averaging can be performed along arbitrarily aligned surfaces. This study considers a particular case in which isopycnal averaging is performed at constant height. Thus, this new isopycnal averaging follows isopycnals as they meander horizontally at constant z. Height information is now retained at the cost of losing latitudinal information. The advantage of this averaging is that it avoids the problem of giving a surface that is too warm. Associated with this new isopycnal averaging, a “vertical” transport streamfunction in (ρ, z) space can be defined, in analogy to the conventional meridional overturning streamfunction in (y, ρ) space. Here in Part I, this constant-height isopycnal averaging is explained and illustrated in an idealized zonal channel model. In Part II the relationship between the two different isopycnal averagings and the Eulerian mean eddy flux divergence is explored.
A Study of the Iceland–Faeroe Frontal Variability Using the Multiscale Energy and Vorticity Analysis
Authors: Liang Xiang San , Robinson Allan R. 
Published: January 2005

Abstract
The multiscale nonlinear interactive Iceland–Faeroe frontal (IFF) variability during 14–22 August 1993 is investigated for complex dynamics with the localized multiscale energy and vorticity analysis (MS-EVA). In terms of multiscale window transform, the cold meandering intrusion observed in the IFF experiment is represented on a mesoscale window. The resulting mesoscale energetics for the deep layer show an isolated center of transfer of potential energy from the large-scale window into the mesoscale window in the study domain. This large-to-mesoscale potential energy transfer, or BC for short, is a baroclinic instability indicator by the MS-EVA-based stability theory. Signatures on other energetics maps and the reconstructed mesoscale structures all support this baroclinic instability. On the BC map, the transfer hotspot originally resides near the western boundary. It travels along the front into the interior domain in a form of convective instability and then, on 19 August, changes into another instability that is absolute in character. Correspondingly, disturbances switch from a spatial growing pattern into a time growing mode, culminating on 21 August, the day just before the intrusion matures. The whole process lasts for about five days, limited within a small horizontal region and beneath a depth of approximately 150 m. By interaction analysis, the energy locally gained from this process goes to the submesoscale window as well, but most of it remains in the mesoscale window, serving to fuel the growth of the meandering intrusion.