bluuebunny/crossref_metadata_2025_split huggingface dataset:
NF-κB Serves as a Cellular Sensor of Kaposi's Sarcoma-Associated Herpesvirus Latency and Negatively Regulates K-Rta by Antagonizing the RBP-Jκ Coactivator
Authors: Izumiya Yoshihiro , Izumiya Chie , Hsia Datsun , Ellison Thomas J. , Luciw Paul A. , Kung Hsing-Jien 
Published: February 2009

ABSTRACT
Successful viral replication is dependent on a conducive cellular environment; thus, viruses must be sensitive to the state of their host cells. We examined the idea that an interplay between viral and cellular regulatory factors determines the switch from Kaposi's sarcoma-associated herpesvirus (KSHV) latency to lytic replication. The immediate-early gene product K-Rta is the first viral protein expressed and an essential factor in reactivation; accordingly, this viral protein is in a key position to serve as a viral sensor of cellular physiology. Our approach aimed to define a host transcription factor, i.e., host sensor, which modulates K-Rta activity on viral promoters. To this end, we developed a panel of reporter plasmids containing all 83 putative viral promoters for a comprehensive survey of the response to both K-Rta and cellular transcription factors. Interestingly, members of the NF-κB family were shown to be strong negative regulators of K-Rta transactivation for all but two viral promoters (Ori-RNA and K12). Recruitment of K-Rta to the ORF57 and K-bZIP promoters, but not the K12 promoter, was significantly impaired when NF-κB expression was induced. Many K-Rta-responsive promoters modulated by NF-κB contain the sequence of the RBP-Jκ binding site, a major coactivator which anchors K-Rta to target promoters via consensus motifs which overlap with that of NF-κB. Gel shift assays demonstrated that NF-κB inhibits the binding of RBP-Jκ and forms a complex with RBP-Jκ. Our results support a model in which a balance between K-Rta/RBP-Jκ and NF-κB activities determines KSHV reactivation. An important feature of this model is that the interplay between RBP-Jκ and NF-κB on viral promoters controls viral gene expression mediated by K-Rta.
HLA Footprints on Human Immunodeficiency Virus Type 1 Are Associated with Interclade Polymorphisms and Intraclade Phylogenetic Clustering
Authors: Matthews Philippa C. , Leslie Alasdair J. , Katzourakis Aris , Crawford Hayley , Payne Rebecca , Prendergast Andrew , Power Karen , Kelleher Anthony D. , Klenerman Paul , Carlson Jonathan , Heckerman David , Ndung'u Thumbi , Walker Bruce D. , Allen Todd M. , Pybus Oliver G. , Goulder Philip J. R. 
Published: February 2009

ABSTRACT

The selection of escape mutations has a major impact on immune control of infections with viruses such as human immunodeficiency virus (HIV). Viral evasion of CD8
+
T-cell responses leaves predictable combinations of escape mutations, termed HLA “footprints.” The most clearly defined footprints are those associated with HLA alleles that are linked with successful control of HIV, such as HLA-B*57. Here we investigated the extent to which HLA footprint sites in HIV type 1 (HIV-1) are associated with viral evolution among and within clades. First, we examined the extent to which amino acid differences between HIV-1 clades share identity with sites of HLA-mediated selection pressure and observed a strong association, in particular with respect to sites of HLA-B selection (
P
< 10
−6
). Similarly, the sites of amino acid variability within a clade were found to overlap with sites of HLA-selected mutation. Second, we studied the impact of HLA selection on interclade phylogeny. Removing the sites of amino acid variability did not significantly affect clade-specific clustering, reflecting the central role of founder effects in establishing distinct clades. However, HLA footprints may underpin founder strains, and we show that amino acid substitutions between clades alter phylogeny, underlining a potentially substantial role for HLA in driving ongoing viral evolution. Finally, we investigated the impact of HLA selection on within-clade phylogeny and demonstrate that even a single HLA allele footprint can result in significant phylogenetic clustering of sequences. In conclusion, these data highlight the fact that HLA can be a strong selection force for both intra- and interclade HIV evolution at a population level.
The Epstein-Barr Virus (EBV) Deubiquitinating Enzyme BPLF1 Reduces EBV Ribonucleotide Reductase Activity
Authors: Whitehurst Christopher B. , Ning Shunbin , Bentz Gretchen L. , Dufour Florent , Gershburg Edward , Shackelford Julia , Langelier Yves , Pagano Joseph S. 
Published: February 2009

ABSTRACT

A newly discovered virally encoded deubiquitinating enzyme (DUB) is strictly conserved across the
Herpesviridae
. Epstein-Barr virus (EBV) BPLF1 encodes a tegument protein (3,149 amino acids) that exhibits deubiquitinating (DUB) activity that is lost upon mutation of the active-site cysteine. However, targets for the herpesviral DUBs have remained elusive. To investigate a predicted interaction between EBV BPLF1 and EBV ribonucleotide reductase (RR), a functional clone of the first 246 N-terminal amino acids of BPLF1 (BPLF1 1-246) was constructed. Immunoprecipitation verified an interaction between the small subunit of the viral RR2 and BPLF1 proteins. In addition, the large subunit (RR1) of the RR appeared to be ubiquitinated both in vivo and in vitro; however, ubiquitinated forms of the small subunit, RR2, were not detected. Ubiquitination of RR1 requires the expression of both subunits of the RR complex. Furthermore, coexpression of RR1 and RR2 with BPLF1 1-246 abolishes ubiquitination of RR1. EBV RR1, RR2, and BPLF1 1-246 colocalized to the cytoplasm in HEK 293T cells. Finally, expression of enzymatically active BPLF1 1-246 decreased RR activity, whereas a nonfunctional active-site mutant (BPLF1 C61S) had no effect. These results indicate that the EBV deubiquitinating enzyme interacts with, deubiquitinates, and influences the activity of the EBV RR. This is the first verified protein target of the EBV deubiquitinating enzyme.
Ganglioside-Linked Terminal Sialic Acid Moieties on Murine Macrophages Function as Attachment Receptors for Murine Noroviruses
Authors: Taube Stefan , Perry Jeffrey W. , Yetming Kristen , Patel Sagar P. , Auble Heather , Shu Liming , Nawar Hesham F. , Lee Chang Hoon , Connell Terry D. , Shayman James A. , Wobus Christiane E. 
Published: February 2009

ABSTRACT

Noroviruses are the major cause of nonbacterial gastroenteritis in humans. However, little is known regarding the norovirus life cycle, including cell binding and entry. In contrast to human noroviruses, the recently discovered murine norovirus 1 (MNV-1) readily infects murine macrophages and dendritic cells in culture. Many viruses, including the related feline calicivirus, use terminal sialic acids (SA) as receptors for infection. Therefore, we tested whether SA moieties play a role during MNV-1 infection of murine macrophages. Competition with SA-binding lectins and neuraminidase treatment led to a reduction in MNV-1 binding and infection in cultured and primary murine macrophages, suggesting a role for SA during the initial steps of the MNV-1 life cycle. Because SA moieties can be attached to glycolipids (i.e., gangliosides), we next determined whether MNV-1 uses gangliosides during infection. The gangliosides GD1a, GM1, and asialo-GM1 (GA1) are natural components of murine macrophages. MNV-1 bound to ganglioside GD1a, which is characterized by an SA on the terminal galactose, but not to GM1 or asialo-GM1 in an enzyme-linked immunosorbent assay. The depletion of gangliosides using an inhibitor of glycosylceramide synthase (
d
-
threo
-P4) led to a reduction of MNV-1 binding and infection in cultured and primary murine macrophages. This defect was specifically rescued by the addition of GD1a. A similar phenotype was observed for MNV field strains WU11 (GV/WU11/2005/USA) and S99 (GV/Berlin/2006/DE). In conclusion, our data indicate that MNV can use terminal SA on gangliosides as attachment receptors during binding to murine macrophages.
Epstein-Barr Virus Nuclear Antigen 3C Augments Mdm2-Mediated p53 Ubiquitination and Degradation by Deubiquitinating Mdm2
Authors: Saha Abhik , Murakami Masanao , Kumar Pankaj , Bajaj Bharat , Sims Karen , Robertson Erle S. 
Published: February 2009

ABSTRACTEpstein-Barr virus (EBV) nuclear antigen 3C (EBNA3C) is one of the essential latent antigens for primary B-cell transformation. Previous studies established that EBNA3C facilitates degradation of several vital cell cycle regulators, including the retinoblastoma (pRb) and p27KIPproteins, by recruitment of the SCFSkp2E3 ubiquitin ligase complex. EBNA3C was also shown to be ubiquitinated at its N-terminal residues. Furthermore, EBNA3C can bind to and be degraded in vitro by purified 20S proteasomes. Surprisingly, in lymphoblastoid cell lines, EBNA3C is extremely stable, and the mechanism for this stability is unknown. In this report we show that EBNA3C can function as a deubiquitination enzyme capable of deubiquitinating itself in vitro as well as in vivo. Functional mapping using deletion and point mutational analysis showed that both the N- and C-terminal domains of EBNA3C contribute to the deubiquitination activity. We also show that EBNA3C efficiently deubiquitinates Mdm2, an important cellular proto-oncogene, which is known to be overexpressed in several human cancers. The data presented here further demonstrate that the N-terminal domain of EBNA3C can bind to the acidic domain of Mdm2. Additionally, the N-terminal domain of EBNA3C strongly stabilizes Mdm2. Importantly, EBNA3C simultaneously binds to both Mdm2 and p53 and can form a stable ternary complex; however, in the presence of p53 the binding affinity of Mdm2 toward EBNA3C was significantly reduced, suggesting that p53 and Mdm2 might share a common overlapping domain of EBNA3C. We also showed that EBNA3C enhances the intrinsic ubiquitin ligase activity of Mdm2 toward p53, which in turn facilitated p53 ubiquitination and degradation. Thus, manipulation of the oncoprotein Mdm2 by EBNA3C potentially provides a favorable environment for transformation and proliferation of EBV-infected cells.
Crystal Structure of Dengue Virus Type 1 Envelope Protein in the Postfusion Conformation and Its Implications for Membrane Fusion
Authors: Nayak Vinod , Dessau Moshe , Kucera Kaury , Anthony Karen , Ledizet Michel , Modis Yorgo 
Published: February 2009

ABSTRACT
Dengue virus relies on a conformational change in its envelope protein, E, to fuse the viral lipid membrane with the endosomal membrane and thereby deliver the viral genome into the cytosol. We have determined the crystal structure of a soluble fragment E (sE) of dengue virus type 1 (DEN-1). The protein is in the postfusion conformation even though it was not exposed to a lipid membrane or detergent. At the domain I-domain III interface, 4 polar residues form a tight cluster that is absent in other flaviviral postfusion structures. Two of these residues, His-282 and His-317, are conserved in flaviviruses and are part of the “pH sensor” that triggers the fusogenic conformational change in E, at the reduced pH of the endosome. In the fusion loop, Phe-108 adopts a distinct conformation, forming additional trimer contacts and filling the bowl-shaped concavity observed at the tip of the DEN-2 sE trimer.
Optimal Transactivation by Epstein-Barr Nuclear Antigen 1 Requires the UR1 and ATH1 Domains
Authors: Singh Gyanendra , Aras Siddhesh , Zea Arnold H. , Koochekpour Shahriar , Aiyar Ashok 
Published: February 2009

ABSTRACT
Epstein-Barr nuclear antigen 1 (EBNA1) is essential for Epstein-Barr virus to immortalize naïve B cells. EBNA1 transactivates viral promoters for genes that are necessary for immortalization when it is bound to a cluster of 20 cognate binding sites, termed the family of repeats. A region of EBNA1 from amino acids (aa) 40 to 89, termed linking region 1 (LR1), has been identified previously as being sufficient for transactivation. LR1 contains two domains that are conserved in the EBNA1 orthologs of other gamma herpesviruses. The first of these, termed unique region 1 (UR1), corresponds to aa 65 to 89 of EBNA1. UR1 is necessary for transactivation and contains a conserved recognition site for cyclic AMP-dependent protein kinase (PKA), corresponding to serine 78 of EBNA1. We have pharmacologically modulated PKA activity to determine if PKA controls EBNA1's ability to transactivate. Our results indicate that PKA activators and inhibitors do not affect transactivation by EBNA1. In addition, site-directed mutagenesis demonstrates that transactivation is not influenced by the phosphorylation status of serine 78 in the UR1 domain. The second conserved domain within LR1 is a glycine-arginine repeat, corresponding to aa 40 to 54 of EBNA1. This domain, termed ATH1, functions as an AT-hook, a DNA-binding motif found in architectural transcription factors such as HMGA1a. We demonstrate that deletion of the ATH1 domain decreases EBNA1 transactivation ability, which is consistent with a transcriptional role for ATH1. Furthermore, transactivation is restored when ATH1 is replaced by equivalent AT-hook motifs from HMGA1a. Our data strongly indicate a role for AT-hooks in EBNA1's ability to transactivate, a function necessary for EBV to immortalize naïve B-cells.
Hepatitis B Virus Replication and Release Are Independent of Core Lysine Ubiquitination
Authors: Garcia Mayra L. , Byfield Rushelle , Robek Michael D. 
Published: February 2009

ABSTRACT
Ubiquitin conjugation to lysine residues regulates a variety of protein functions, including endosomal trafficking and degradation. While ubiquitin plays an important role in the release of many viruses, the requirement for direct ubiquitin conjugation to viral structural proteins is less well understood. Some viral structural proteins require ubiquitin ligase activity, but not ubiquitin conjugation, for efficient release. Recent evidence has shown that, like other viruses, hepatitis B virus (HBV) requires a ubiquitin ligase for release from the infected cell. The HBV core protein contains two lysine residues (K7 and K96), and K96 has been suggested to function as a potential ubiquitin acceptor site based on the fact that previous studies have shown that mutation of this amino acid to alanine blocks HBV release. We therefore reexamined the potential connection between core lysine ubiquitination and HBV replication, protein trafficking, and virion release. In contrast to alanine substitution, we found that mutation of K96 to arginine, which compared to alanine is more conserved but also cannot mediate ubiquitin conjugation, does not affect either virus replication or virion release. We also found that the core lysine mutants display wild-type sensitivity to the antiviral activity of interferon, which demonstrates that ubiquitination of core lysines does not mediate the interferon-induced disruption of HBV capsids. However, mutation of K96 to arginine alters the nuclear-cytoplasmic distribution of core, leading to an accumulation in the nucleolus. In summary, these studies demonstrate that although ubiquitin may regulate the HBV replication cycle, these mechanisms function independently of direct lysine ubiquitination of core protein.
EMC STUDIES USING THE SIMULATION FRAMEWORK OF PANDA
Authors:   FOR THE PANDA COLLABORATION, BIEGUN ALEKSANDRA 
Published: February 2009

The Anti-Proton ANnihilation at DArmstadt (PANDA) experiment proposed at the Facility for Antiproton and Ion Research (FAIR) in Darmstadt (Germany) will perform a high-precision spectroscopy of charmonium and exotic hadrons, such as hybrids, glueballs and hypernuclei. A highly intense beam of anti-protons provided by High Energy Storage Ring (HESR) with an unprecedented resolution will scan a mass range of 2 to 5.5 GeV/c2. In preparation for experiments with PANDA, careful and large-scale simulation studies need to be performed in the coming years to determine analysis strategies, to provide feedback for the design, construction and performance optimisation of individual detector components and to design methods for the calibration and interpretation of the experimental results. Results of a simulation for the ElectroMagnetic Calorimeter (EMC), built from lead tungstate (PWO) crystals and placed inside the Target Spectrometer (TS), are presented. The simulations were carried out using the PandaRoot framework, which is based on ROOT and being developed by the PANDA collaboration.
FORWARD SPECTROMETER OF PANDA — REQUIREMENTS AND SOLUTIONS
Authors:   FOR THE PANDA COLLABORATION, WROŃSKA ALEKSANDRA 
Published: February 2009

PANDA is a future antiproton experiment designed to study fundamental questions of hadron and nuclear physics. It will work as a fixed-target facility, hence – due to the Lorentz boost – the distribution of reaction products will be strongly forward-peaked, in particular for the near-threshold measurements. Thus, the Forward Spectrometer, covering the most forward angles (θlab < 10°) is one of the key components of PANDA. In this contribution, current design of the Forward Spectrometer is presented. Spectrometer components, including dipole magnet, tracking detectors, electromagnetic and hadron calorimeter, muon counters, RICH detector and TOF system are discussed. Results of simulations are shown along with tests of the prototype detectors performed in a high-rate environment.
RECENT NA48/2 RESULTS ON Ke4 AND K3π DECAYS AND DETERMINATION OF THE ππ SCATTERING LENGTHS
Authors:   FOR THE NA48/2 COLLABORATION, BIZZETI ANDREA 
Published: February 2009

Large samples of K± → 3π and K± → π+π-e±ν (Ke4) decays have been collected by the NA48/2 experiment at CERN SPS. At the π+π- threshold, the π0π0 invariant mass spectrum of the decay K± → π±π0π0 xhibits a Wigner cusp, from which the S-wave ππ scattering lengths are extracted with high precision. The same scattering lengths are also independently determined from the accurate measurement of the form factors in the Ke4 decay K± → π+π-e±ν.
ANALYZING POWERS MEASUREMENT FOR d - p ELASTIC SCATTERING AT THE INTERNAL TARGET STATION OF NUCLOTRON
Authors: KURILKIN P. K. , SUDA K. , UESAKA T. , LADYGIN V. P. , GURCHIN YU. V. , YU. ISUPOV A. , ITOH K. , JANEK M. , KARACHUK J.-T. , KAWABATA T. , KHRENOV A. N. , KISELEV A. S. , KIZKA V. A. , KLIMAN J. , KRASNOV V. A. , LADYGINA N. B. , LIVANOV A. N. , MAEDA Y. , MALAKHOV A. I. , MATOUCEK V. , MORHAC M. , REZNIKOV S. G. , SAKAGUCHI S. , SAKAI H. , SASAMOTO Y. , SEKIGUCHI K. , SHIKHALEV M. A. , TURZO I. , VASILIEV T. A. , WITAŁA H. 
Published: February 2009

Analyzing powers measurement Ay, Ayy and Axx for the d - p elastic scattering were performed at the Internal Target Station of Nuclotron at JINR at Ed = 880 and 2000 MeV. These data are necessary to obtain the information on the 3NF structure and the relativistic effects. They are also important for development of the efficient deuteron beam polarimetry at high energies. The results of the analyzing powers at Ed = 880 MeV covered the angular range from 60 to 140° in the c.m.s. are compared with several theoretical calculations. The preliminary data on the analyzing powers measurement Ay, Ayy at Ed = 2000 MeV are discussed.
An Awkward, but Potent, Fit Photographs and Political Narratives of the Tianjin Incidents During the Sino-Japanese Conflict, November 1931
Authors: Sheehan Brett 
Published: February 2009

AbstractIn November 1931, Japanese-hired Chinese 'plainclothesmen' attacked strategic locations in the Chinese portions of Tianjin leading to the eruption of a mini war for most of the month. At the time the Chinese and Japanese sides engaged in a bitter dispute about the basic facts of the events. The use of photographs in the service of these conflicting narratives shows that on the Chinese side coverage emphasised the link between the plainclothesmen and Japan by contrasting Japanese aggression with Chinese victimhood. Photographs in Japanese sources portrayed an enclosed and claustrophobic Japanese concession surrounded by threats from Chinese agitators goaded on by the Nationalist government. In all versions, photographic content and political narrative often fit awkwardly. Captions, juxtaposition and accompanying news stories placed otherwise cryptic photographs in larger political narratives. The ubiquitous use of photographs indicates a belief in their power which derived from both their claim on veracity and their ability to create an emotional conenction with the viewer. As a political tool, the photograph functioned in public mass media where readers hungered for the poignant and sensational. In the end, veracity and emotional charge, political narrative and sensationalist photo, militarism and wartime reporting were all inextricably linked.
Changing Socio-Economic Environments, Housing Culture and New Urban Segregation in Seoul
Authors: Gelézeau Valérie 
Published: February 2009

AbstractThe paper focuses on the recent transformation of the urban housing culture in South Korea through a geographical analysis of Seoulite apartment complexes (ap'at'ŭu tanji). The paper first analyses the changes in housing policy and the housing production system since the late 1970s, which have long been oriented mainly towards the middle and upper-middle classes. Not only have the lower-income classes been excluded from this new apartment culture, it also seems that the housing situation testifies to the partial failure of the so-called filtering process (in which the benefits of development are purported to spread through society from top to bottom). The paper then analyses the post-Asian crisis transformation of the housing environment in the city, where housing redevelopment projects are concentrated in highly speculative areas (Kangnam) and new forms of luxury condominium apartments (such as the Acroville complex) are appearing. At the same time, older apartment complexes are faced with more and more maintenance problems as well as with the constant pressure to reduce management fees. As in many world metropolises, emerging 'gated communities' and increasing social spatial segregations seem to characterise the housing culture and geography of Seoul today.
Water and Moisture Absorption and Thickness Swelling Behavior in Polypropylene/Wood Flour/Glass Fiber Hybrid Composites
Authors: Mohebby Behbood , Younesi Hamed , Ghotbifar Alireza , Kazemi-Najafi Saeed 
Published: February 2009

The purpose of the current research was to investigate water/moisture absorption and associated thickness swelling and their rates in hybrid wood flour/E-glass fiber/propylene composite immersed in water, exposed to steam, and the influence of application of the glass fiber as well as maleic-anhydride-polypropylene (MAPP 2%) as coupling agent on those properties. The sample strips with 10 mm thickness and 70 mm width were made by using a laboratory twin-screw extruder. The specimens were immersed in water and exposed to steam for 4320 min to determine the water/moisture absorption and the thickness swelling as well as their rates in the composites. Results revealed that application of the glass fibers increased in the water/moisture absorption significantly in the hybrid composites due to formed micro-gaps in interfaces between wood flour and the glass fibers. However, application of the coupling agent (MAPP 2%) significantly reduced the micro-gaps and diminished the water/moisture absorption as well as the related thickness swelling in the hybrid composites.