bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telomerase Activation by Human Papillomavirus Type 16 E6 Protein: Induction of Human Telomerase Reverse Transcriptase Expression through Myc and GC-Rich Sp1 Binding Sites
Authors: Oh Stephen T. , Kyo Saturo , Laimins Laimonis A. 
Published: July 2002

ABSTRACT

High-risk human papillomaviruses (HPVs) immortalize keratinocytes by disrupting the retinoblastoma protein (Rb)/p16 pathway and activating telomerase. The E7 oncoprotein targets Rb, while the E6 oncoprotein induces telomerase activity in human keratinocytes. This study has examined the mechanism by which E6 activates telomerase. Expression of human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase, was found to be increased in keratinocytes stably expressing HPV type 16 E6, suggesting that E6 acts to increase hTERT transcription. hTERT expression and telomerase activity were activated to significantly higher levels in cells expressing both E6 and E7 than in cells expressing E6 alone. This indicates that E7 may augment E6-mediated activation of hTERT transcription. In transient-transfection assays using hTERT reporters, the induction of hTERT expression by E6 was found to be mediated by a 258-bp fragment of the hTERT promoter, proximal to the ATG initiation codon. Previous studies have demonstrated that overexpression of Myc can activate hTERT expression, suggesting that Myc may be a mediator of E6-mediated hTERT induction. However, in cells stably expressing E6, no strict correlation between the level of Myc and the activation of hTERT was found. Consistent with this observation, mutation of the two Myc binding sites in the hTERT promoter only modestly reduced responsiveness to E6 in transient reporter assays. This indicates that activation of Myc-dependent transcription is not essential for E6-mediated upregulation of hTERT expression. The hTERT promoter also contains five GC-rich elements that can bind Sp1. Mutation of these sites within the 258-bp fragment partially reduced hTERT induction by E6. However, when mutations in the Sp1 sites were combined with the mutated Myc binding sites, all activation by E6 was lost. This indicates that it is the combinatorial binding of factors to Myc and Sp1
cis
elements that is responsible for hTERT induction by E6.
Virus Reconstituted from Infectious Bacterial Artificial Chromosome (BAC)-Cloned Murine Gammaherpesvirus 68 Acquires Wild-Type Properties In Vivo Only after Excision of BAC Vector Sequences
Authors: Adler Heiko , Messerle Martin , Koszinowski Ulrich H. 
Published: July 2002

ABSTRACT

We studied the in vivo biological properties of viruses reconstituted from the genome of murine gammaherpesvirus 68 (MHV-68) cloned as an infectious bacterial artificial chromosome (BAC). Recombinant virus RγHV68A98.01, containing BAC vector sequences, is attenuated in vivo as determined by (i) viral titers in the lungs during the acute phase of infection, (ii) the extent of splenomegaly, and (iii) the number of latently infected spleen cells reactivating virus in an ex vivo reactivation assay. Since the BAC vector sequences were flanked by
lox
P sites, passaging the virus in fibroblasts expressing Cre recombinase resulted in the generation of recombinant virus RγHV68A98.02, with biological properties comparable to those of wild-type MHV-68. On the basis of these data we conclude (i) that excision of BAC vector sequences from cloned MHV-68 genomes is critical for reconstitution of the wild-type phenotypic properties of this virus and (ii) that the BAC-cloned MHV-68 genome is suitable for the construction of mutants and mutant libraries whose phenotypes can be reliably assessed in vivo.
Evidence that
Equine Rhinitis A Virus
VP1 Is a Target of Neutralizing Antibodies and Participates Directly in Receptor Binding
Authors: Warner Simone , Hartley Carol A. , Stevenson Rachel A. , Ficorilli Nino , Varrasso Annalisa , Studdert Michael J. , Crabb Brendan S. 
Published: July 2002

ABSTRACT

Equine rhinitis A virus
(ERAV) is a respiratory pathogen of horses and is classified as an
Aphthovirus
, the only non-
Foot-and-mouth disease virus
(FMDV) member of this genus. In FMDV, virion protein 1 (VP1) is a major target of protective antibodies and is responsible for viral attachment to permissive cells via an RGD motif located in a distal surface loop. Although both viruses share considerable sequence identity, ERAV VP1 does not contain an RGD motif. To investigate antibody and receptor-binding properties of ERAV VP1, we have expressed full-length ERAV VP1 in
Escherichia coli
as a glutathione
S
-transferase (GST) fusion protein (GST-VP1). GST-VP1 reacted specifically with antibodies present in serum from a rabbit immunized with purified ERAV virions and also in convalescent-phase sera from horses experimentally infected with ERAV. An antiserum raised in rabbits to GST-VP1 reacted strongly with viral VP1 and effectively neutralized ERAV infection in vitro. Using a flow cytometry-based binding assay, we found that GST-VP1, but not other GST fusion proteins, bound to cell surface receptors. This binding was reduced in a dose-dependent manner by the addition of purified ERAV virions, demonstrating the specificity of this interaction. A separate cell-binding assay also implicated GST-VP1 in receptor binding. Importantly, anti-GST-VP1 antibodies inhibited the binding of ERAV virions to Vero cells, suggesting that these antibodies exert their neutralizing effect by blocking viral attachment. Thus ERAV VP1, like its counterpart in FMDV, appears to be both a target of protective antibodies and involved directly in receptor binding. This study reveals the potential of recombinant VP1 molecules to serve as vaccines and diagnostic reagents for the control of ERAV infections.
Infection and Activation of Monocytes by Marburg and Ebola Viruses
Authors: Ströher Ute , West Elmar , Bugany Harald , Klenk Hans-Dieter , Schnittler Hans-Joachim , Feldmann Heinz 
Published: July 2002

ABSTRACTIn this study we investigated the effects of Marburg virus and Ebola virus (species Zaire and Reston) infections on freshly isolated suspended monocytes in comparison to adherent macrophages under culture conditions. Our data showed that monocytes are permissive for both filoviruses. As is the case in macrophages, infection resulted in the activation of monocytes which was largely independent of virus replication. The activation was triggered similarly by Marburg and Ebola viruses, species Zaire and Reston, as indicated by the release of the proinflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor α, and IL-6 as well as the chemokines IL-8 and gro-α. Our data suggest that infected monocytes may play an important role in the spread of filoviruses and in the pathogenesis of filoviral hemorrhagic disease.
Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox
Authors: Jackson Ronald J. , Ramsay Alistair J. , Christensen Carina D. , Beaton Sandra , Hall Diana F. , Ramshaw Ian A. 
Published: July 2002

ABSTRACTGenetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is characterized by an effective natural killer (NK) response and the early onset of a strong CD8+cytotoxic T-lymphocyte (CTL) response in resistant mice. We have investigated the influence of virus-expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4-expressing virus developed symptoms of acute mousepox accompanied by high mortality, similar to the disease seen when genetically sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mousepox. These data therefore suggest that virus-encoded IL-4 not only suppresses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.
Recombinant Human Parvovirus B19 Vectors: Erythrocyte P Antigen Is Necessary but Not Sufficient for Successful Transduction of Human Hematopoietic Cells
Authors: Weigel-Kelley Kirsten A. , Yoder Mervin C. , Srivastava Arun 
Published: July 2002

ABSTRACT
The blood group P antigen, known to be abundantly expressed on erythroid cells, has been reported to be the cellular receptor for parvovirus B19. We have described the development of recombinant parvovirus B19 vectors with which high-efficiency, erythroid lineage-restricted transduction can be achieved (S. Ponnazhagan, K. A. Weigel, S. P. Raikwar, P. Mukherjee, M. C. Yoder, and A. Srivastava, J. Virol. 72:5224–5230, 1998). However, since a low-level transduction of nonerythroid cells could also be detected and since P antigen is expressed in nonerythroid cells, we reevaluated the role of P antigen in the viral binding and entry into cells. Cell surface expression analyses revealed that ∼75% of primary human bone marrow mononuclear erythroid cells and ∼31% of cells in the nonerythroid population were positive for P antigen. Two human erythroleukemia cell lines, HEL and K562, and a human promyelocytic leukemia cell line, HL-60, were also examined for P antigen expression and binding and entry of the vector. HEL and K562 cells showed intermediate levels, whereas HL-60 cells demonstrated high levels of expression of P antigen. However, the efficiency of vector binding to these cells did not correlate with P antigen expression. Moreover, despite P antigen positivity and efficient viral binding, HEL, K562, and HL-60 cells could not be transduced with the vector. Low levels of P antigen expression could also be detected in two primary cell types, human umbilical vein endothelial cells (HUVEC) and normal human lung fibroblasts (NHLF). In addition, vector binding occurred in both cell types and was inhibited by globoside, indicating the involvement of P antigen in virus binding to these cells. These primary cells could be efficiently transduced with the recombinant vector. These data suggest that (i) P antigen is expressed on a variety of cell types and is involved in binding of parvovirus B19 to human cells, (ii) the level of P antigen expression does not correlate with the efficiency of viral binding, (iii) P antigen is necessary but not sufficient for parvovirus B19 entry into cells, and (iv) parvovirus B19 vectors can be used to transduce HUVEC and NHLF. These studies further suggest the existence of a putative cellular coreceptor for efficient entry of parvovirus B19 into human cells.
Group A Rotavirus Infection and Age-Dependent Diarrheal Disease in Rats: a New Animal Model To Study the Pathophysiology of Rotavirus Infection
Authors: Ciarlet Max , Conner Margaret E. , Finegold Milton J. , Estes Mary K. 
Published: July 2002

ABSTRACT

Group A rotaviruses are major pathogens causing acute gastroenteritis in children and animals. To determine if group A rotavirus replicates and induces disease in rats, antibody-negative Lewis neonatal or adult rats were inoculated orally with tissue culture-adapted human (Wa, WI61, and HAL1166), simian (rhesus rotavirus [RRV] and SA11), bovine (WC3), lapine (ALA), or porcine (OSU) rotavirus strains, wild-type murine (EC
wt
) rotavirus strain, or phosphate-buffered saline (PBS). Rotavirus infection in rats was evaluated by (i) clinical findings, (ii) virus antigen shedding or infectious virus titers in the feces or intestinal contents measured by enzyme-linked immunosorbent assay or fluorescent-focus assay, (iii) histopathological changes in the small intestine, (iv) distribution of rotavirus antigen in small-intestine sections by immunofluorescence, and (v) growth rate. Rotavirus infection of 5-day-old but not ≥21-day-old rats resulted in diarrhea that lasted from 1 to 10 days postinoculation. The severity of disease and spread of infection to naÏve littermates differed depending on the virus strain used for inoculation. The duration of virus antigen shedding following infection was considerably prolonged (up to 10 days) in neonatal rats compared to that in 21-day-old rats (1 or 2 days). Based on lack of virus antigen shedding and disease induction, the murine EC
wt
rotavirus was the only strain tested that did not infect rats. Histopathological changes in the small-intestine mucosa of 5-day-old RRV-inoculated rats but not of PBS-inoculated rats was limited to extensive enterocyte vacuolation in the ileum. In RRV-inoculated neonatal rats, rotavirus antigen was detected in the epithelial cells on the upper half of the intestinal villi of the jejunum and ileum. In addition, infection of neonatal rats with RRV but not with PBS resulted in reduced weight gain. Rats infected with group A rotaviruses provide a new animal model with unique features amenable to investigate rotavirus pathogenesis and the molecular mechanisms of intestinal development, including physiological factors that may regulate age-dependent rotavirus-induced diarrhea.
Functional Interaction between the pp71 Protein of Human Cytomegalovirus and the PML-Interacting Protein Human Daxx
Authors: Hofmann Heike , Sindre Hilde , Stamminger Thomas 
Published: July 2002

ABSTRACT
The tegument protein pp71 (UL82) of human cytomegalovirus (HCMV) has previously been shown to transactivate the major immediate-early enhancer-promoter of HCMV. Furthermore, this protein is able to enhance the infectivity of viral DNA and to accelerate the infection cycle, suggesting an important regulatory function during viral replication. To gain insight into the underlying mechanisms that are used by pp71 to exert these pleiotropic effects, we sought for cellular factors interacting with pp71 in a yeast two-hybrid screen. Here, we report the isolation of the human Daxx (hDaxx) protein as a specific interaction partner of HCMV pp71. hDaxx, which was initially described as an adapter protein involved in apoptosis regulation, has recently been identified as a nuclear protein that interacts and colocalizes with PML in the nuclear domain ND10. In order to assess whether pp71 can also be detected in ND10 structures, a vector expressing pp71 in fusion with the green fluorescent protein was used for transfection of human fibroblasts. This revealed a colocalization of pp71 with the ND10 proteins PML and Sp100. In addition, cotransfection of a hDaxx expression vector resulted in an enhanced recruitment of pp71 to ND10. Targeting of pp71 to nuclear dots could also be observed in infected human fibroblasts in the absence of de novo viral protein synthesis. Moreover, cotransfection experiments revealed that pp71-mediated transactivation of the major immediate-early enhancer-promoter was synergistically enhanced in the presence of hDaxx. These results suggest an important role of hDaxx for pp71 protein function.
Safety and Immunogenicity in Neonatal Mice of a HyperattenuatedListeriaVaccine Directed against Human Immunodeficiency Virus
Authors: Rayevskaya Marina , Kushnir Natasha , Frankel Fred R. 
Published: July 2002

ABSTRACTCD8+T cells are a major component of the adaptive response of a host to infections by viruses and other intracellular pathogenic agents. However, because of the intrinsic immaturity of the immune system of neonatal animals, neonates are highly sensitive to a variety of pathogens and may be unable to respond in a protective manner. Here we explore whether a hyperattenuated strain ofListeria monocytogenesthat can be used as a live vaccine vector in adults is safe and able to induce an effective response in neonates. We answer both questions affirmatively.
Distribution and determinants of trihalomethane concentrations in indoor swimming pools
Authors: Chu H , Nieuwenhuijsen M J 
Published: July 2002

Objectives: For many decades chlorination has been used as a major disinfectant process for public drinking and swimming pool water in many countries. However, there has been rising concern over the possible link between disinfectant byproducts (DBPs) and adverse reproductive outcomes. The purpose of this study was to estimate the concentrations of trihalomethanes (THMs) in some indoor swimming pools in London and their variation within and between pools and any correlation with other factors.Methods: Water samples were collected from eight different indoor swimming pools in London. A total of 44 pool samples were collected and analysed for total organic content (TOC) and THMs. Water and air temperature were measured along with the pH during the collection of pool samples. The level of turbulence and the number of people in the pool at the time were also assessed.Results: The geometric mean concentration for all swimming pools of TOC was 5.8 mg/l, of total THMs (TTHMs) 132.4 μg/l, and for chloroform 113.3 μg/l. There was a clear positive linear correlation between the number of people in the swimming pool and concentrations of TTHMs and chloroform (r=0.7, p<0.01), and a good correlation between concentrations of TOC and TTHMs (r=0.5, p<0.05) and water temperature and concentrations of TTHMs (r=0.5, p<0.01). There was a larger variation in THMs within pools than between pools.Conclusion: Relatively high concentrations of THMs were found in London's indoor swimming pools. The levels correlated with the number of people in the pool, water temperature, and TOC. The variation in concentrations of THMs was greater within pools than between pools.
Hepatocellular adenomatosis associated with hereditary haemochromatosis
Authors: Radhi J M , Loewy J 
Published: July 2002

Summary
A young healthy man presented with abdominal pain following an accidental fall. Imaging studies and laparoscopy revealed multiple yellowish well-defined hepatic lesions. Liver biopsies showed hepatic adenomas and iron overload. Laboratory investigation confirmed a diagnosis of hereditary haemochromatosis. To our knowledge this represents the first report of an association of hepatic adenomatosis and primary haemochromatosis.
Antiplatelet use in interventional cardiology
Authors: Brodison Adrian , Katira Ravish , More Ranjit S , Chauhan Anoop 
Published: July 2002

Summary
Thrombosis within the target vessel is one of the most feared complications associated with coronary intervention, as it is often associated with severe adverse clinical sequelae. This thrombosis is mediated via the activation and aggregation of platelets and therefore considerable effort has been directed at ways of inhibiting platelet function. It is now mandatory to consider the use of two and often three different antiplatelet agents, particularly when intracoronary stents are inserted. Using these regimes, many of the adverse clinical outcomes associated with platelet activation can be reduced.
VECTOR ALGORITHMS FOR APPROXIMATE STRING MATCHING
Authors: BERGERON ANNE , HAMEL SYLVIE 
Published: July 2002

Vector algorithms allow the computation of an output vector r = r1 r2 ⋯ rm given an input vector e = e1 e2 ⋯ em in a bounded number of operations, independent of m the length of the vectors. The allowable operations are usually restricted to bit-wise operations available in processors, including shifts and binary addition with carry. These restrictions imple that the existence of a vector algorithm for a particular problem opens the way to extremely fast implementations, using the inherent parallelism of bit-wise operations. This paper presents general results on the existence and construction of vertor algorithms, with a particular focus on problems arising from computational biology. We show that efficient vector algorithms exist for the problem of approximate string matching with arbitrary weighted distances, generalizing a previous result by G. Myers. We also characterize a class of automata for which vector algorithms can be automatically derived from the transition table of the automata.
INVERSE DISPERSION RELATION OF BZ-WAVES IN NONSTATIONARY GELS
Authors: HANKE W. 
Published: July 2002

The behavior of wave propagation, as well that of isolated waves as that of self-sustained activity, in excitable media is characterized by the dispersion relation of the system. For the Belousov–Zhabotinsky (BZ)-reaction as by far the best described system, a number of theoretical considerations and experimental investigations do exist. From the theoretical point of view the dispersion relation of the BZ-reaction has two branches, an upper "fast" or stable branch typified by singular solutions and a lower "slow" branch whose solutions are regular, with a connection between the two branches, defining the smallest possible period and the absolute refractory period of the system. Experimental data are usually located on the upper branch giving higher propagation velocity at increasing period. Only one set of results was published in the early 1970s with velocity being an increasing function of frequency. This set of data was stated to be "difficult to believe" in later papers.We now present here a more detailed study of a BZ-system with a dispersion relation with an increasing velocity at decreasing period, verifying the existence of an "inverse" dispersion relation at least in the nonstationary gels we have used.
On modeling of information retrieval concepts in vector spaces
Authors: Wong S. K.M. , Ziarko W. , Raghavan V. V. , Wong P. C.N. 
Published: July 2002

The Vector Space Model (VSM) has been adopted in information retrieval as a means of coping with inexact representation of documents and queries, and the resulting difficulties in determining the relevance of a document relative to a given query. The major problem in employing this approach is that the explicit representation of term vectors is not known a priori. Consequently, earlier researchers made the assumption that the vectors corresponding to terms are pairwise orthogonal. Such an assumption is clearly unrealistic. Although attempts have been made to compensate for this assumption by some separate, corrective steps, such methods are ad hoc and, in most cases, formally inconsistent.
In this paper, a generalization of the VSM, called the GVSM, is advanced. The developments provide a solution not only for the computation of a measure of similarity (correlation) between terms, but also for the incorporation of these similarities into the retrieval process.
The major strength of the GVSM derives from the fact that it is theoretically sound and elegant. Furthermore, experimental evaluation of the model on several test collections indicates that the performance is better than that of the VSM. Experiments have been performed on some variations of the GVSM, and all these results have also been compared to those of the VSM, based on inverse document frequency weighting. These results and some ideas for the efficient implementation of the GVSM are discussed.
Three-dimensional computer display
Authors: Ophir D. , Spinrad R. J. 
Published: July 2002

A stereographic display terminal has been produced using the raster display (BRAD) recently developed at Brookhaven. The system uses a rotating refresh memory to feed standard television monitors.
To produce a stereographic display the computer calculates the projected video images of an object, viewed from two separated points. The resulting video maps are stored on separate refresh bands of the rotating memory. The two output signals are connected to separate color guns of a color television monitor, thus creating a superimposed image on the screen. Optical separation is achieved by viewing the image through color filters.
The display is interactive and can be viewed by a large group of people at the same time.