bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Differentiation-Specific Factor CDP/Cut Represses Transcription and Replication of Human Papillomaviruses through a Conserved Silencing Element
Authors: O'Connor Mark J. , Stünkel Walter , Koh Choon-Heng , Zimmermann Holger , Bernard Hans-Ulrich 
Published: April 2009

ABSTRACT

The life cycles of human papillomaviruses (HPVs) are intimately linked to the differentiation program of infected stratified epithelia, with both viral gene expression and replication being maintained at low levels in undifferentiated basal cells and increased upon host cell differentiation. We recently identified, in HPV-16, a negative regulatory element between the epithelial-cell-specific enhancer and the E6 promoter that is capable of silencing E6 promoter activity, and we termed this element a papillomavirus silencing motif (PSM) and the unknown cellular factor that bound to it PSM binding protein (PSM-BP). Here we show that the homologous genomic segments of six other distantly related genital HPV types contain a PSM that binds PSM-BP and is capable of repressing transcription. Conservation of the PSM suggests that it is indispensable for the HPV life cycle. Purification, electrophoretic mobility shift assay experiments, and the use of specific antibodies proved that the cellular factor PSM-BP is identical to a previously described transcriptional repressor, the CCAAT displacement protein (CDP), also referred to as the human Cut protein (Cut). CDP/Cut repression of HPV-16 may stem from the modification of specifically positioned nucleosomes, as suggested by transcriptional stimulation under the influence of the histone deacetylase inhibitor trichostatin A. CDP/Cut is an important developmental regulator in several different tissues. It was recently shown that CDP/Cut is expressed in basal epithelial cells but not in differentiated primary keratinocytes. This suggests the possibility that repression by PSM couples HPV transcription to the stratification of epithelia. In each of the studied HPV types, the two CDP/Cut binding sites of PSM overlap with the known or presumed binding sites of the replication initiator protein E1. Transfection of CDP/Cut expression vectors into cells that support HPV-16 or HPV-31 replication leads to the elimination of viral episomes. Similarly, two PSM-like motifs overlapping the E1 binding site of bovine papillomavirus type 1 bind CDP/Cut, and CDP/Cut overexpression reduces the copy number of episomally replicating BPV-1 genomes in mouse fibroblasts. CDP/Cut appears to be a master regulator of HPV transcription and replication during epithelial differentiation, and PSMs are important
cis
-responsive targets of this repressor.
Polyuridylated mRNA Synthesized by a Recombinant Influenza Virus Is Defective in Nuclear Export
Authors: Poon Leo L. M. , Fodor Ervin , Brownlee George G. 
Published: April 2009

ABSTRACT
The poly(A) tail of influenza virus mRNA is synthesized by reiterative copying of a U track near the 5′ end of the virion RNA (vRNA) template by the viral RNA polymerase. We have engineered a novel influenza A/WSN/33 virus which contains a neuraminidase (NA) vRNA with its U track mutated into an A track. Instead of synthesizing poly(A)-tailed NA mRNA, this novel virus synthesizes poly(U)-tailed NA mRNA. In infected cells, most poly(U)-tailed NA mRNA was retained in the nucleus, while most control polyadenylated NA mRNA was transported to the cytoplasm. These results suggest that the poly(A) tail is important for efficient nuclear export of NA mRNA. The mutant virus produced a reduced amount of NA and showed an attenuated phenotype, suggesting that poly(A) signal mutants of this type might be useful as potential live attenuated virus vaccines. In addition, this virus mutant might provide a useful model to further elucidate the basic mechanisms of mRNA nuclear export.
Identification of the Novel K15 Gene at the Rightmost End of the Kaposi's Sarcoma-Associated Herpesvirus Genome
Authors: Choi Joong-Kook , Lee Bok-Soo , Shim Sung N. , Li Mengtao , Jung Jae U. 
Published: April 2009

ABSTRACTKaposi's sarcoma-associated herpesvirus (KSHV) encodes a distinct open reading frame called K15 at a position equivalent to the gene encoding LMP2A of Epstein-Barr virus (EBV). K15 isolates from body cavity-based lymphoma (BCBL) cells exhibited a dramatic sequence variation and a complex splicing pattern. However, all K15 alleles are organized similarly with the potential SH2 and SH3 binding motifs in their cytoplasmic regions. Northern blot analysis showed that K15 was weakly expressed in latently infected BCBL-1 cells, and the level of its expression was significantly induced by tetradecanoyl phorbol acetate stimulation. K15 encoded 40- to 55-kDa proteins, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and was localized at the cytoplasm and plasma membrane. To demonstrate the signal-transducing activity of the K15 protein, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8α polypeptide was replaced with that of KSHV K15. While the CD8-K15 chimera was not capable of eliciting cellular signal transduction upon stimulation with an anti-CD8 antibody, it significantly inhibited B-cell receptor signaling, as evidenced by a suppression of tyrosine phosphorylation and intracellular calcium mobilization. This inhibition required the putative SH2 or SH3 binding motif in the cytoplasmic region of K15. Biochemical study of CD8-K15 chimeras showed that the cytoplasmic region of K15 was constitutively tyrosine phosphorylated and that the tyrosine residue within the putative SH2 binding motif of K15 was a primary site of phosphorylation. These results demonstrate that KSHV K15 resembles LMP2A in genomic location, splicing pattern, and protein structure and by the presence of functional signal-transducing motifs in the cytoplasmic region. Thus, KSHV K15 is likely a distant evolutionary relative of EBV LMP2A.
Role of the Cytoplasmic Tail of Ecotropic Moloney Murine Leukemia Virus Env Protein in Fusion Pore Formation
Authors: Melikyan Grigory B. , Markosyan Ruben M. , Brener Sofya A. , Rozenberg Yanina , Cohen Fredric S. 
Published: April 2009

ABSTRACT
Fusion between cells expressing envelope protein (Env) of Moloney murine leukemia virus and target cells were studied by use of video fluorescence microscopy and electrical capacitance measurements. When the full-length 632-amino-acid residue Env was expressed, fusion did not occur at all for 3T3 cells as target and only somewhat for XC6 cells. Expression of Env 616*—a construct of Env with the last 16 amino acid residues (617 to 632; the R peptide) deleted from its C terminus to match the proteolytically cleaved Env produced during viral budding—resulted in high levels of fusion. Env 601*, lacking the entire cytoplasmic tail (CT) (identified by hydrophobicity), also led to fusion. Truncation of an additional six residues (Env 595*) abolished fusion. The kinetics of forming fusion pores did not depend on whether cells were first prebound at 4°C and the time until fusion measured after the temperature was raised to 37°C or whether cells were first brought into contact at 37°C and the time until fusion immediately measured. This similarity in kinetics indicates that binding is accomplished quickly compared to subsequent steps in fusion. The fusion pores formed by Env 601* and Env 616* had the same initial size and enlarged in similar manners. Thus, once the R peptide is removed, the CT is not needed for fusion and does not affect formed pores. However, residues 595 to 601 are required for fusion. It is suggested here that the ectodomain and membrane-spanning domain of Env are directly responsible for fusion and that the R peptide affects their configurations at some point during the fusion process, thereby indirectly controlling fusion.
Small Dense Nuclear Bodies Are the Site of Localization of Herpes Simplex Virus 1 U
L
3 and U
L
4 Proteins and of ICP22 Only When the Latter Protein Is Present
Authors: Markovitz Nancy S. , Roizman Bernard 
Published: April 2009

ABSTRACT

The herpes simplex virus 1 U
L
3 and U
L
4 open reading frames are expressed late in infection and are not essential for viral replication in cultured cells in vitro. An earlier report showed that the U
L
4 protein colocalizes with the products of the α22/U
S
1.5 genes in small nuclear dense bodies. Here we report that the U
L
3 protein also colocalized in these small nuclear dense bodies and the localization of U
L
3 and U
L
4 proteins in these bodies required the presence of α22/U
S
1.5 genes. In cells infected with a mutant lacking intact α22/U
S
1.5 genes, U
L
3 was diffused throughout the nucleus even though the overall accumulation of the γ2 U
L
3 protein was decreased. The results suggest that ICP22 acts both as a regulator of U
L
3 accumulation and as the structural component and anchor of these small dense nuclear bodies.
env
Sequences of Simian Immunodeficiency Viruses from Chimpanzees in Cameroon Are Strongly Related to Those of Human Immunodeficiency Virus Group N from the Same Geographic Area
Authors: Corbet Sylvie , Müller-Trutwin Michaela C. , Versmisse Pierre , Delarue Severine , Ayouba Ahidjo , Lewis John , Brunak Soren , Martin Paul , Brun-Vezinet Françoise , Simon François , Barre-Sinoussi Françoise , Mauclere Philippe 
Published: April 2009

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) group N from Cameroon is phylogenetically close, in
env
, to the simian immunodeficiency virus (SIV) cpz-gab from Gabon and SIVcpz-US of unknown geographic origin. We screened 29 wild-born Cameroonian chimpanzees and found that three (Cam3, Cam4, and Cam5) were positive for HIV-1 by Western blotting. Mitochondrial DNA sequence analysis demonstrated that Cam3 and Cam5 belonged to
Pan troglodytes troglodytes
and that Cam4 belonged to
P. t. vellerosus
. Genetic analyses of the viruses together with serological data demonstrated that at least one of the two
P. t. troglodytes
chimpanzees (Cam5) was infected in the wild, and revealed a horizontal transmission between Cam3 and Cam4. These data confirm that
P. t. troglodytes
is a natural host for HIV-1-related viruses. Furthermore, they show that SIVcpz can be transmitted in captivity, from one chimpanzee subspecies to another. All three SIVcpz-cam viruses clustered with HIV-1 N in
env
. The full Cam3 SIVcpz genome sequence showed a very close phylogenetic relationship with SIVcpz-US, a virus identified in a
P. t. troglodytes
chimpanzee captured nearly 40 years earlier. Like SIVcpz-US, SIVcpz-cam3 was closely related to HIV-1 N in
env
, but not in
pol
, supporting the hypothesis that HIV-1 N results from a recombination event. SIVcpz from chimpanzees born in the wild in Cameroon are thus strongly related in
env
to HIV-1 N from Cameroon, demonstrating the geographic coincidence of these human and simian viruses and providing a further strong argument in favor of the origin of HIV-1 being in chimpanzees.
α-Glucosidase Inhibitors Reduce Dengue Virus Production by Affecting the Initial Steps of Virion Morphogenesis in the Endoplasmic Reticulum
Authors: Courageot Marie-Pierre , Frenkiel Marie-Pascale , Duarte Dos Santos Claudia , Deubel Vincent , Desprès Philippe 
Published: April 2009

ABSTRACT
We report that endoplasmic reticulum α-glucosidase inhibitors have antiviral effects on dengue (DEN) virus. We found that glucosidase inhibition strongly affects productive folding pathways of the envelope glycoproteins prM (the intracellular glycosylated precursor of M [membrane protein]) and E (envelope protein): the proper folding of prM bearing unprocessed N-linked oligosaccharide is inefficient, and this causes delayed formation of prME heterodimer. The complexes formed between incompletely folded prM and E appear to be unstable, leading to a nonproductive pathway. Inhibition of α-glucosidase-mediated N-linked oligosaccharide trimming may thus prevent the assembly of DEN virus by affecting the early stages of envelope glycoprotein processing.
Identification of a Bovine Coronavirus Packaging Signal
Authors: Cologna Raymond , Hogue Brenda G. 
Published: April 2009

ABSTRACT

A region of the bovine coronavirus (BCV) genome that functions as a packaging signal has been cloned. The 291-nucleotide clone shares 72% homology with the region of mouse hepatitis coronavirus (MHV) gene
1b
that contains the packaging signal. RNA transcripts were packaged into both BCV and MHV virions when the cloned region was appended to a noncoronavirus RNA. This is the first identification of a BCV packaging signal. The data demonstrate that the BCV genome contains a sequence that is conserved at both the sequence and functional levels, thus broadening our insight into coronavirus packaging.
Analysis of HCF, the Cellular Cofactor of VP16, in Herpes Simplex Virus-Infected Cells
Authors: LaBoissière Sylvie , O'Hare Peter 
Published: April 2009

ABSTRACT

Herpes simplex virus (HSV) immediate-early (IE) gene expression is initiated via the recruitment of the structural protein VP16 onto specific sites upstream of each IE gene promoter in a multicomponent complex (TRF.C) that also includes the cellular proteins Oct-1 and HCF. In vitro results have shown that HCF binds directly to VP16 and stabilizes TRF.C. Results from transfection assays have also indicated that HCF is involved in the nuclear import of VP16. However, there have been no reports on the role or the fate of HCF during HSV type 1 (HSV-1) infection. Here we show that the intracellular distribution of HCF is dramatically altered during HSV-1 infection and that the protein interacts with and colocalizes with VP16. Moreover, viral protein synthesis and replication were significantly reduced after infection of a BHK-21-derived temperature-sensitive cell line (
ts
BN67) which contains a mutant HCF unable to associate with VP16 at the nonpermissive temperature. Intracellular distribution of HCF and of newly synthesized VP16 in
ts
BN67-infected cells was similar to that observed in Vero cells, suggesting that late in infection the trafficking of both proteins was not dependent on their association. We constructed a stable cell line (
ts
BN67r) in which the temperature-sensitive phenotype was rescued by using an epitope-tagged wild-type HCF. In HSV-1-infected
ts
BN67r cells at the nonpermissive temperature, direct binding of HCF to VP16 was observed, but virus protein synthesis and replication were not restored to levels observed at the permissive temperature or in wild-type BHK cells. Together these results indicate that the factors involved in compartmentalization of VP16 alter during infection and that late in infection, VP16 and HCF may have additional roles reflected in their colocalization in replication compartments.
The Continuous Spectrum in Baroclinic Models with Uniform Potential Vorticity Gradient and Ekman Damping
Authors: de Vries Hylke 
Published: April 2009

Abstract
Analytic solutions of the continuous spectrum are obtained for quasigeostrophic models in which the basic-state meridional potential vorticity (PV) gradient is uniform but nonzero. The modes that form the continuous spectrum—continuum modes—are baroclinically neutral, singular solutions of the linear dynamical equations, which have an interior critical level. Although most inviscid shear flows support continuous spectra, previous studies have largely been restricted to models in which the interior PV gradient is zero. In that situation, continuum modes are formed by a superposition of boundary potential temperature anomalies and an interior PV δ function at the critical level. Here it is shown how a nonzero interior PV gradient and Ekman damping nontrivially affect the vertical structure of continuum modes. A consideration of the perturbation PV further rationalizes their vertical structure.
Lightning Flash Rates as an Indicator of Tropical Cyclone Genesis in the Eastern North Pacific
Authors: Leary Lesley A. , Ritchie Elizabeth A. 
Published: April 2009

AbstractLightning flashes in convective tropical clusters of the eastern North Pacific Ocean are detected by the Long-Range Lightning Detection Network and are analyzed for temporal patterns in electrical activity. The rates of lightning flash discharge in the 2006 season are analyzed for both tropical cyclones and nondeveloping cloud clusters to 1) determine if there is a difference in the convective activity of these two populations and 2) find a level of electrical activity that constitutes development in a particular system. Convective activity is associated with tropical cyclogenesis and thus we use the rate of electrical discharge as a proxy for convection associated with the likelihood of organization of individual cloud clusters into a tropical depression strength system. On the basis of the rates of lightning flashes in the cloud clusters, four levels of development are defined, ranging from non- and partially developing to fully developing cloud clusters. The levels of development are further supported by the analysis of other remotely sensed observations, such as surface scatterometer winds, that allow for the description of the mesoscale and large-scale circulation patterns in which the cloud clusters are embedded. It is found that lightning flash rates distinguish those cloud clusters that do not fully develop into tropical depressions from those that do. Receiver operating characteristic curves for these groupings are calculated, and a level of flash rate can be chosen that gives a probability of detection of 67% for a false-alarm rate of 24%.
Drainage demands of domestic washrooms in Hong Kong
Authors: Wong LT , Mui KW 
Published: April 2009

Drainage demand estimation for an effective and healthy drainage stack design is examined in this study. Empirical expressions that incorporate building occupant load, simultaneous usage patterns and discharge flow attenuation along a horizontal pipe into the probable drainage load determination for a stack serving a number of domestic washrooms as installed in typical high-rise buildings in Hong Kong are proposed. Patterns of probable drainage demand and probable discharge flow in the stack are determined via Bayesian analysis and Monte Carlo simulations, respectively. The study outcome enables more effective sizing of a drainage stack for some residential buildings in a dense urban environment. Practical application: Providing a mathematical model for drainage load calculations, this study is a useful tool to aid drainage stack sizing for some high-rise residential buildings.
Molecular network of the comprehensive multiple sclerosis brain-lesion proteome
Authors: Satoh JI , Tabunoki H , Yamamura T 
Published: April 2009

Background A recent proteomics study of multiple sclerosis (MS) lesion-specific proteome profiling clearly revealed a pivotal role of coagulation cascade proteins in chronic active demyelination. However, among thousands of proteins examined, nearly all of remaining proteins are yet to be characterized in terms of their implications in MS brain-lesion development. Methods By the systems biology approach using four different pathway analysis tools of bioinformatics, we studied molecular networks and pathways of the proteome dataset of acute plaques, chronic active plaques (CAP), and chronic plaques (CP). Results The database search on Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein analysis through evolutionary relationships (PANTHER) indicated the relevance of extracellular matrix (ECM)–mediated focal adhesion and integrin signaling to CAP and CP proteome. KeyMolnet disclosed a central role of the complex interaction among diverse cytokine signaling pathways in brain-lesion development at all disease stages, as well as a role of integrin signaling in CAP and CP. Ingenuity pathway analysis (IPA) identified the network constructed with a wide range of ECM components, such as collagen, type I α1, type I α2, type VI α2, type VI α3, fibronectin 1, fibulin 2, laminin α1, vitronectin, and heparan sulfate proteoglycan, as one of the networks highly relevant to CAP proteome. Conclusions Although four distinct platforms produced diverse results, they commonly suggested a role of ECM and integrin signaling in development of chronic lesions of MS. These in silico observations indicate that the selective blockade of the interaction between ECM and integrins in brain lesions in situ would be a target for therapeutic intervention in MS.
The relationship between handedness and risk of multiple sclerosis
Authors: Gardener H , Munger K , Chitnis T , Spiegelman D , Ascherio A 
Published: April 2009

Background Left-handedness has been studied as a marker for in-utero exposure to sex steroid hormones, and an increased risk of autoimmune and immune disorders among left-handed individuals has been suggested. Objective This study examines the relationship between hand preference and risk of multiple sclerosis, a presumed autoimmune disorder of unknown etiology. Methods The study population comprised participants in the Nurses’ Health Study, an ongoing prospective cohort study of 121,701 female nurses in the United States with followup from 1976 to 2002. The nurses were asked to report their natural hand preference (right, left, ambidextrous, forced to change). Results During followup 210 incident cases with multiple sclerosis were confirmed. A 62% increased risk of multiple sclerosis was observed among women who were naturally left handed as compared to those who were naturally right handed (95% CI: 1.04–2.53). Conclusions This study suggests a modest increase in risk of multiple sclerosis among left-handed women. Further investigation of this relationship is suggested in other populations including both males and females. While the current results suggest that prenatal exposure to sex hormones may play a role in multiple sclerosis risk, direct examination of the relationship between in-utero hormone exposure and hand preference is necessary before any conclusions can be drawn.
Helping offenders into employment
Authors: Vennard Julie , Hedderman Carol 
Published: April 2009

The Probation Service has, for some years, worked with external service providers in partnership. One strand of this work has involved collaboration with voluntary sector organizations in helping offenders into education training and employment (ETE). Underlying this work is a slim but important evidence base, which shows that offending diminishes when offenders gain employment, and that being in work may trigger longer term desistance. Drawing on an evaluation of a government-sponsored `Employment Pathfinder' and on other relevant research, the article argues that recent governmental pressure to contract out services, and to adhere to certain `what works in reducing re-offending' principles, has given rise to tension within this collaboration attributable to conflicting ideology and practice. Specifically, this has created a context in which there is limited scope to adopt practices which are informed by knowledge about `what works' in getting people into employment. A less prescriptive approach from the centre about what should be delivered, and how, would restore effective teamwork and might also open up probation practice to empirical and theoretical insights into the desistance process. Wider implications of these findings for the future involvement of organizations with expertise in the provision of services for offenders are discussed.