bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Antiviral Pathway That Mediates Hepatitis C Virus Replicon Interferon Sensitivity through ADAR1
Authors: Taylor Deborah R. , Puig Montserrat , Darnell Miriam E. R. , Mihalik Kathleen , Feinstone Stephen M. 
Published: April 2005

ABSTRACT
While many clinical hepatitis C virus (HCV) infections are resistant to alpha interferon (IFN-α) therapy, subgenomic in vitro self-replicating HCV RNAs (HCV replicons) are characterized by marked IFN-α sensitivity. IFN-α treatment of replicon-containing cells results in a rapid loss of viral RNA via translation inhibition through double-stranded RNA-activated protein kinase (PKR) and also through a new pathway involving RNA editing by an adenosine deaminase that acts on double-stranded RNA (ADAR1). More than 200 genes are induced by IFN-α, and yet only a few are attributed with an antiviral role. We show that inhibition of both PKR and ADAR1 by the addition of adenovirus-associated RNA stimulates replicon expression and reduces the amount of inosine recovered from RNA in replicon cells. Small inhibitory RNA, specific for ADAR1, stimulated the replicon 40-fold, indicating that ADAR1 has a role in limiting replication of the viral RNA. This is the first report of ADAR's involvement in a potent antiviral pathway and its action to specifically eliminate HCV RNA through adenosine to inosine editing. These results may explain successful HCV replicon clearance by IFN-α in vitro and may provide a promising new therapeutic strategy for HCV as well as other viral infections.
Compartmentalization of Hepatitis C Virus Genotypes between Plasma and Peripheral Blood Mononuclear Cells
Authors: Roque-Afonso Anne-Marie , Ducoulombier Delphine , Di Liberto Gaëtana , Kara Rachid , Gigou Michele , Dussaix Elisabeth , Samuel Didier , Féray Cyrille 
Published: April 2005

ABSTRACT

Differences in hepatitis C virus (HCV) variants of the highly conserved 5′ untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%];
P
< 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%;
P
< 0.001). Cloning of the 5′ UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.
Stimulation of Poliovirus Synthesis in a HeLa Cell-Free In Vitro Translation-RNA Replication System by Viral Protein 3CD
pro
Authors: Franco David , Pathak Harsh B. , Cameron Craig E. , Rombaut Bart , Wimmer Eckard , Paul Aniko V. 
Published: April 2005

ABSTRACT

The plus-strand RNA genome of poliovirus serves three distinct functions in the life cycle of the virus. The RNA is translated and then replicated, and finally the progeny RNAs are encapsidated. These processes can be faithfully reproduced in a HeLa cell-free in vitro translation-RNA replication system that produces viable poliovirus. We have previously observed a stimulation of virus synthesis when an mRNA, encoding protein 3CD
pro
, is added to the translation-RNA replication reactions of poliovirus RNA. Our aim in these experiments was to further define the factors that affect the stimulatory activity of 3CD
pro
in virus synthesis. We observed that purified 3CD
pro
protein also enhances virus synthesis by about 100-fold but has no effect on the translation of the polyprotein. Optimal stimulation is observed only when 3CD
pro
is present early in the incubation period. The stimulation, however, is abolished by a mutation either in the RNA binding domain of 3CD
pro
, 3C
pro
R84S/I86A, or by each of two groups of complementary mutations R455A/R456A and D339A/S341A/D349A at interface I in the 3D
pol
domain of 3CD
pro
. Surprisingly, virus synthesis is strongly inhibited by the addition of both 3C
pro
and 3CD
pro
at the beginning of incubation. We also examined the effect of other viral or cellular proteins on virus synthesis in the in vitro system. No enhancement of virus synthesis occurred with viral proteins 3BC, 3ABC, 3BCD, 3D
pol
, and 3C
pro
or with cellular protein PCBP2. These results suggest that 3CD
pro
has to be present in the reaction at the time the replication complexes are assembled and that both the 3C
pro
and 3D
pol
domains of the protein are required for its activity that stimulates virus production.
Comparative Genomics of Foot-and-Mouth Disease Virus
Authors: Carrillo C. , Tulman E. R. , Delhon G. , Lu Z. , Carreno A. , Vagnozzi A. , Kutish G. F. , Rock D. L. 
Published: April 2005

ABSTRACT

Here we present complete genome sequences, including a comparative analysis, of 103 isolates of foot-and-mouth disease virus (FMDV) representing all seven serotypes and including the first complete sequences of the SAT1 and SAT3 genomes. The data reveal novel highly conserved genomic regions, indicating functional constraints for variability as well as novel viral genomic motifs with likely biological relevance. Previously undescribed invariant motifs were identified in the 5′ and 3′ untranslated regions (UTR), as was tolerance for insertions/deletions in the 5′ UTR. Fifty-eight percent of the amino acids encoded by FMDV isolates are invariant, suggesting that these residues are critical for virus biology. Novel, conserved sequence motifs with likely functional significance were identified within proteins L
pro
, 1B, 1D, and 3C. An analysis of the complete FMDV genomes indicated phylogenetic incongruities between different genomic regions which were suggestive of interserotypic recombination. Additionally, a novel SAT virus lineage containing nonstructural protein-encoding regions distinct from other SAT and Euroasiatic lineages was identified. Insights into viral RNA sequence conservation and variability and genetic diversity in nature will likely impact our understanding of FMDV infections, host range, and transmission.
Human Circovirus TT Virus Genotype 6 Expresses Six Proteins following Transfection of a Full-Length Clone
Authors: Qiu Jianming , Kakkola Laura , Cheng Fang , Ye Chaoyang , Söderlund-Venermo Maria , Hedman Klaus , Pintel David J. 
Published: April 2005

ABSTRACT
The expression profile of the circovirus TTV has not yet been fully characterized. In this paper, we show that following transfection of a full-length viral clone of TTV genotype 6, each of the three virally encoded mRNAs is translated from two initiating AUGs, and therefore, the TTV genome generates at least six proteins. Localization studies of hemagglutinin-tagged versions of these proteins in fixed cells, and green fluorescent protein-tagged versions of these proteins in living cells, expressed following transfection, demonstrated that two were primarily nuclear, two were primarily cytoplasmic, and two were found throughout the cell.
Replication-Defective Adenovirus Serotype 5 Vectors Elicit Durable Cellular and Humoral Immune Responses in Nonhuman Primates
Authors: Santra Sampa , Seaman Michael S. , Xu Ling , Barouch Dan H. , Lord Carol I. , Lifton Michelle A. , Gorgone Darci A. , Beaudry Kristin R. , Svehla Krisha , Welcher Brent , Chakrabarti Bimal K. , Huang Yue , Yang Zhi-Yong , Mascola John R. , Nabel Gary J. , Letvin Norman L. 
Published: April 2005

ABSTRACT
The magnitude and durability of immune responses induced by replication-defective adenovirus serotype 5 (ADV5) vector-based vaccines were evaluated in the simian-human immunodeficiency virus/rhesus monkey model. A single inoculation of recombinant ADV5 vector constructs induced cellular and humoral immunity, but the rapid generation of neutralizing anti-Ad5 antibodies limited the immunity induced by repeated vector administration. The magnitude and durability of the immune responses elicited by these vaccines were greater when they were delivered as boosting immunogens in plasmid DNA-primed monkeys than when they were used as single-modality immunogens. Therefore, administration of ADV5-based vectors in DNA-primed subjects may be a preferred use of this vaccine modality for generating long-term immune protection.
Selection for Human Immunodeficiency Virus Type 1 Envelope Glycosylation Variants with Shorter V1-V2 Loop Sequences Occurs during Transmission of Certain Genetic Subtypes and May Impact Viral RNA Levels
Authors: Chohan Bhavna , Lang Dorothy , Sagar Manish , Korber Bette , Lavreys Ludo , Richardson Barbra , Overbaugh Julie 
Published: April 2005

ABSTRACT
Designing an effective human immunodeficiency virus type 1 (HIV-1) vaccine will rely on understanding which variants, from among the myriad of circulating HIV-1 strains, are most commonly transmitted and determining whether such variants have an Achilles heel. Here we show that heterosexually acquired subtype A HIV-1 envelopes have signature sequences that include shorter V1-V2 loop sequences and fewer predicted N-linked glycosylation sites relative to the overall population of circulating variants. In contrast, recently transmitted subtype B variants did not, and this was true for cases where the major risk factor was homosexual contact, as well as for cases where it was heterosexual contact. This suggests that selection during HIV-1 transmission may vary depending on the infecting subtype. There was evidence from 23 subtype A-infected women for whom there was longitudinal data that those who were infected with viruses with fewer potential N-linked glycosylation sites in V1-V2 had lower viral set point levels. Thus, our study also suggests that the extent of glycosylation in the infecting virus could impact disease progression.
Structural Elements of the tRNA TΨC Loop Critical for Nucleocytoplasmic Transport Are Important for Human Immunodeficiency Virus Type 1 Primer Selection
Authors: Kelly Nathan J. , Morrow Casey D. 
Published: April 2005

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) selects a host cell tRNA as the primer for the initiation of reverse transcription. In a previous study, transport of the intact tRNA from the nucleus to the cytoplasm during tRNA biogenesis was shown to be a requirement for the selection of the tRNA primer by HIV-1. To further examine the importance of tRNA structure for transport and the selection of the primer, yeast tRNA
Phe
mutants were designed such that the native tRNA structure would be disrupted to various extents. The capacity of the mutant tRNA
Phe
to complement a defective HIV-1 provirus that relies on the expression of yeast tRNA
Phe
for infectivity was determined. We found a direct relationship between intact tRNA conformation and the capacity to be selected by HIV-1 for use in reverse transcription. tRNA
Phe
mutants that retained the capacity for nucleocytoplasmic transport, indicative of overall intact conformation, complemented the defective provirus. The mutant tRNAs were not aminoacylated, and the levels of complementation were lower than that for wild-type tRNA
Phe
, which did undergo transport and aminoacylation. Taken together, these results demonstrate that HIV-1 primer selection is most dependent on a tRNA structure necessary for nucleocytoplasmic transport, consistent with primer selection occurring in the cytoplasm at or near the site of protein synthesis.
Identification of a Peach Latent Mosaic Viroid Hairpin Able To Act as a Dicer-Like Substrate
Authors: Landry Patricia , Perreault Jean-Pierre 
Published: April 2005

ABSTRACT
The ability of several viroids to induce posttranscriptional gene silencing has been demonstrated; however, the structure recognized by the Dicer enzyme(s) responsible for the initiation of this mechanism remains a mystery. Here, we show that the hairpin known to be implicated in the replication of peach latent mosaic viroid has the ability to trigger the Dicer enzyme(s). This domain, which is composed of a succession of several small stems separated by symmetrical bulges, is reminiscent of the precursor micro-RNAs.
Cyclooxygenase 2 expression in nasopharyngeal carcinoma: immunohistochemical findings and potential implications
Authors: Tan K-B , Putti T C 
Published: April 2005

Background:Cyclooxygenase 2 (COX-2), an inducible prostaglandin synthase, participates in inflammatory and neoplastic processes. It is expressed by various tumours and contributes to carcinogenesis. Notably, COX-2 inhibitors appear to have tumour suppressor effects and are being evaluated in clinical trials.Aims:To investigate COX-2 expression in nasopharyngeal carcinoma (NPC), a common tumour in parts of Asia, and to discuss potential implications.Methods:Eighty five cases of NPC were reviewed. COX-2 immunohistochemistry and semiquantitative assessment of expression in nasopharyngeal biopsies were performed. Because COX-2 is proangiogenic, tumour microvessel density was also assessed with the use of CD31 immunohistochemistry.Results:Histologically, 78 NPCs were undifferentiated, six were non-keratinising, and one was keratinising. Thirty nine NPCs had adjacent dysplastic epithelium. COX-2 expression was noted in 60 NPCs, 14 of 39 samples of dysplastic epithelium, and only one of 25 samples of normal epithelium (p < 0.01). Microvessel density was not significantly different between COX-2 positive and COX-2 negative tumours (p  =  0.774). Tumour COX-2 positivity was not associated with higher tumour stage (p  =  0.423).Conclusion:COX-2 expression is more frequently seen as nasopharyngeal epithelium progresses from normal to dysplastic to carcinoma. This suggests that COX-2 contributes to the multistep process of NPC carcinogenesis. COX-2 represents a therapeutic target for COX-2 inhibitors, and there is thus a basis for the further investigation of this adjuvant treatment modality for NPC. COX-2 inhibitors are known to potentiate the antitumour effects of radiotherapy, which is the primary treatment for NPC.
High expression of Mcl-1 in ALK positive and negative anaplastic large cell lymphoma
Authors: Rust R , Harms G , Blokzijl T , Boot M , Diepstra A , Kluiver J , Visser L , Peh S-C , Lim M , Kamps W A , Poppema S , van den Berg A 
Published: April 2005

Aim:To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL).Methods:Serial analysis of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue samples to confirm the SAGE data.Results:High expression of Mcl-1 was seen in the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-XL, were not detected in the SAGE library. Quantitative RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2 and Bcl-XLin Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-XL, and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK− ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-XLwere expressed infrequently in ALK+ ALCL cases, but were present in a higher proportion of ALK− ALCL cases.Conclusion:The consistent high expression of Mcl-1 in ALK+ and ALK− ALCL suggests that Mcl-1 is the main antiapoptotic protein in this disease. The high frequency of Mcl-1, Bcl-2, and Bcl-XLpositive ALCL cases in the ALK− group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.
Sections of the nipple and quadrants in mastectomy specimens for carcinoma are of limited value: Table 1
Authors: Sikand K , Lee A H S , Pinder S E , Elston C W , Ellis I O 
Published: April 2005

Aim:To assess the value of nipple and quadrant sections in mastectomy specimens for carcinoma in detecting Paget’s disease and multifocal carcinoma.Methods:Two hundred and forty eight consecutive mastectomies performed for carcinoma were reviewed. The presence of Paget’s disease of the nipple and mode of identification of any multifocal carcinoma was recorded.Results:Nipple sections showed Paget’s disease in eight specimens: in five the diagnosis had been made on previous biopsy and in three (1%) this was a new diagnosis. In the 220 specimens in which all four quadrants were sampled, multifocal disease was identified more often in specimens with invasive carcinoma (39 of 186; 21%) than in those with only ductal carcinoma in situ (0 of 34). In specimens with invasive carcinoma, multifocality was identified macroscopically in 20: on microscopy of tumour sections in four, on microscopic examination of quadrant sections in 11, in the nipple in three, and in both quadrant and nipple sections in one. Overall, multifocality was found on microscopic examination of quadrant or nipple sections in 15 of 220 specimens (7%).Conclusions:The low frequency of detection of multifocality or Paget’s disease in nipple and quadrant sections from mastectomy specimens, combined with the fact that such findings do not affect patient management, suggest that nipple and quadrant sections should only be taken if resources permit.
SCHEDULING ON LARGE SCALE DISTRIBUTED PLATFORMS: FROM MODELS TO IMPLEMENTATIONS
Authors: DUTOT PIERRE-FRANÇOIS , EYRAUD LIONEL , MOUNIÉ GRÉGORY , TRYSTRAM DENIS 
Published: April 2005

Today, large scale parallel systems are available at low cost, Many powerful such systems have been installed all over the world and the number of users is always increasing. The difficulty of using them efficiently is growing with the complexity of the interactions between more and more architectural constraints and the diversity of the applications. The design of efficient parallel algorithms has to be reconsidered under the influence of new parameters of such platforms (namely, cluster, grid and global computing) which are characterized by a larger number of heterogeneous processors, often organized in several hierarchical sub-systems. At each step of the evolution of the parallel processing field, researchers designed adequate computational models whose objective was to abstract the real world in order to be able to analyze the behavior of algorithms. In this paper, we will investigate two complementary computational models that have been proposed recently: Parallel Task (PT) and Divisible Load (DL). The Parallel Task (i.e. tasks that require more than one processor for their execution) model is a promising alternative for scheduling parallel applications, especially in the case of slow communication media. The basic idea is to consider the application at a coarse level of granularity. Another way of looking at the problem (which is somehow a dual view) is the Divisible Load model where an application is considered as a collection of a large number of elementary – sequential – computing units that will be distributed among the available resources. Unlike the PT model, the DL model corresponds to a fine level of granularity. We will focus on the PT model, and discuss how to mix it with simple Divisible Load scheduling. As the main difficulty for distributing the load among the processors (usually known as the scheduling problem) in actual systems comes from handling efficiently the communications, these two models of the problem allow us to consider them implicitly or to mask them, thus leading to more tractable problems. We will show that in spite of the enormous complexity of the general scheduling problem on new platforms, it is still useful to study theoretical models. We will focus on the links between models and actual implementations on a regional grid with more than 500 processors.
Gideon—ein Anti-Held? Ein Beitrag zur Auseinandersetzung mit dem sog. 'flawed-hero approach' Am Beispiel Von Jdc. Vi 36–40
Authors: Scherer Andreas 
Published: April 2005

AbstractRecent scholarly investigations concerning the judges narratives tend towards a socalled 'flawed-hero approach'. Especially Gideon has been interpreted as a somewhat ambiguous figure. W. Bluedorn has argued that in Judg. vi 36–40 Gideon wants to cheat YHWH by forcing him to serve Gideon's own selfish desires. Contrary to Bluedorn's view it can be shown, that Gideon is honestly longing for guidance. He needs to be assured of his divine mission, without denying YHWH's sovereignty.
The Fourfold Structure of Job: Variations on a Theme
Authors: Patrick James E. 
Published: April 2005

AbstractThis paper explores further the suggestion of Steinmann that the book of Job displays a consistent preference for fourfold structuring. After restricting the corpus of text to material belonging to the 'narrator', which includes the speech ascriptions introducing each speaker, attention is turned to four different areas. Regular groupings of four are discerned first in the narrative material of the Prologue, introduction to Elihu, and Epilogue, next in the speech ascriptions introducing the speeches of Job, Elihu, and YHWH, then in the speech ascriptions of the dialogue between Job and his three friends, and finally in the book as a whole. Comparisons are then drawn with other typological numbers and with the structure of the speeches themselves, followed by general conclusions concerning the composition of Job.
Evidence for a protective role of the Gardos channel against hemolysis in murine spherocytosis
Authors: De Franceschi Lucia , Rivera Alicia , Fleming Mark D. , Honczarenko Marek , Peters Luanne L. , Gascard Philippe , Mohandas Narla , Brugnara Carlo 
Published: April 2005

AbstractIt has been shown that mice with complete deficiency of all 4.1R protein isoforms (4.1-/-) exhibit moderate hemolytic anemia, with abnormal erythrocyte morphology (spherocytosis) and decreased membrane stability. Here, we characterized the Gardos channel function in vitro and in vivo in erythrocytes of 4.1-/- mice. Compared with wild-type, the Gardos channel of 4.1-/- erythrocytes showed an increase in Vmax (9.75 ± 1.06 vs 6.08 ± 0.09 mM cell × minute; P &lt; .04) and a decrease in Km (1.01 ± 0.06 vs 1.47 ± 1.02 μM; P &lt; .03), indicating an increased sensitivity to activation by intracellular calcium. In vivo function of the Gardos channel was assessed by the oral administration of clotrimazole, a well-characterized Gardos channel blocker. Clotrimazole treatment resulted in worsening of anemia and hemolysis, with decreased red cell survival and increased numbers of circulating hyperchromic spherocytes and microspherocytes. Clotrimazole induced similar changes in 4.2-/- and band 3+/- mice, indicating that these effects of the Gardos channel are shared in different models of murine spherocytosis. Thus, potassium and water loss through the Gardos channel may play an important protective role in compensating for the reduced surface-membrane area of hereditary spherocytosis (HS) erythrocytes and reducing hemolysis in erythrocytes with cytoskeletal impairments. (Blood. 2005;106:1454-1459)