bluuebunny/crossref_metadata_2025_split huggingface dataset:
Change of Tropism of SL3-2 Murine Leukemia Virus, Using Random Mutational Libraries
Authors: Bahrami Shervin , Duch Mogens , Pedersen Finn Skou 
Published: August 2004

ABSTRACT
SL3-2 is a polytropic murine leukemia virus with a limited species tropism. We cloned the envelope gene of this virus, inserted it into a bicistronic vector, and found that the envelope protein differs from other, similar envelope proteins that also utilize the polytropic receptor (Xpr1) in that it is severely impaired in mediating infection of human and mink cells. We found that two adjacent amino acid mutations (G212R and I213T), located in a previously functionally uncharacterized segment of the surface subunit, are responsible for the restricted tropism of the SL3-2 wild-type envelope. By selection from a two-codon library, several hydrophobic amino acids at these positions were found to enable the SL3-2 envelope to infect human TE 671 cells. In particular, an M212/V213 mutant had a titer at least 6 orders of magnitude higher than that of the wild-type envelope for human TE 671 cells and infected human, mink, and murine cells with equal efficiencies. Notably, these two amino acids are not found at homologous positions in known murine leukemia virus isolates. Functional analysis and library selection were done on the basis of sequence and tropism analyses of the SL3-2 envelope gene. Similar approaches may be valuable in the design and optimization of retroviral envelopes with altered tropisms for biotechnological purposes.
Induction of Cellular Immune Responses to Simian Immunodeficiency Virus Gag by Two Recombinant Negative-Strand RNA Virus Vectors
Authors: Nakaya Yurie , Nakaya Takaaki , Park Man-Seong , Cros Jerome , Imanishi Jiro , Palese Peter , García-Sastre Adolfo 
Published: August 2004

ABSTRACTA recombinant Newcastle disease virus (rNDV) expressing simian immunodeficiency virus (SIV) Gag protein (rNDV/SIVgag) was generated. The rNDV/SIVgag virus induced Gag-specific cellular immune responses in mice, leading to a specific anti-Gag antiviral immunity. This was evidenced by the inhibition of growth of recombinant vaccinia virus expressing an identical Gag antigen (rVac/SIVgag) but not of wild-type vaccinia virus in rNDV/SIVgag-immunized mice. Among intravenous, intraperitoneal, or intranasal immunization routes, intranasal administration induced the strongest protective response against challenge with rVac/SIVgag. We further demonstrated that these immune responses were greatly enhanced after booster immunization with recombinant influenza viruses expressing immunogenic portions of SIV Gag. The magnitude of the protective immune response correlated with the levels of cellular immune responses to Gag, which were still evident 9 weeks after immunization. These results suggest that rNDV and influenza virus vectors are suitable candidate vaccines against AIDS as well as against other infectious diseases.
Rabies Virus Stimulates Nitric Oxide Production and CXC Chemokine Ligand 10 Expression in Macrophages through Activation of Extracellular Signal-Regulated Kinases 1 and 2
Authors: Nakamichi Kazuo , Inoue Satoshi , Takasaki Tomohiko , Morimoto Kinjiro , Kurane Ichiro 
Published: August 2004

ABSTRACTMacrophages represent an essential part of innate immunity, and the viral infection of macrophages results in the release of multiple proinflammatory mediators, such as nitric oxide (NO), cytokines, and chemokines. This study was undertaken to define the molecular mechanism of macrophage activation in response to rabies virus (RV) infection. In RAW264 murine macrophage cells, a well-characterized macrophage model, RV replication was strictly restricted, whereas cell proliferation was significantly enhanced upon RV inoculation. Transcriptional analyses for the expression of inducible forms of NO synthase (iNOS), cytokines, and chemokines revealed that RV virions potentiate the gene expression of iNOS and CXC chemokine ligand 10 (CXCL10), a major chemoattractant of T helper cell type 1. However, RV stimulation had little or no effect on the expression profiles of proinflammatory cytokines and other types of chemokines. In macrophages stimulated with UV-inactivated RV virions, as well as infectious viruses, the phosphorylation of extracellular signal-regulated kinase (ERK) 1 and 2, members of the mitogen-activated protein kinase family, was significantly induced. Specific inhibitors of MAPK/ERK kinase reduced the RV-induced production of NO and CXCL10. Furthermore, the RV-induced activation of the ERK1/2 pathway was severely impaired by the neutralization of the endosomal and lysosomal pH environment with lysosomotropic agents, indicating that endocytosis is a key step leading to the activation of ERK1/2 signaling. Taken together, these results suggest that the ERK1/2-mediated signaling pathway plays a cardinal role in the selective activation of macrophages in response to RV virions, thereby regulating cellular functions during virus infection.
Epstein-Barr Virus (EBV) SM Protein Induces and Recruits Cellular Sp110b To Stabilize mRNAs and Enhance EBV Lytic Gene Expression
Authors: Nicewonger John , Suck Garnet , Bloch Donald , Swaminathan Sankar 
Published: August 2004

ABSTRACTPromyelocytic leukemia protein (PML) nuclear bodies or nuclear domain 10s (ND10s) are multiprotein nuclear structures implicated in transcriptional and posttranscriptional gene regulation that are disrupted during replication of many DNA viruses. Interferon increases the size and number of PML nuclear bodies and stimulates transcription of several genes encoding PML nuclear body proteins. Moreover, some PML nuclear body proteins colocalize at sites of viral DNA synthesis and transcription. In this study, the relationship between lytic Epstein-Barr virus (EBV) replication and Sp110b, a PML nuclear body protein, was investigated. Sp110b is shown to physically and functionally interact with the EBV protein SM. SM is expressed early in the EBV replicative cycle and posttranscriptionally increases the level of target EBV lytic transcripts. SM bound to Sp110b via two distinct sites in Sp110b in an RNA-independent manner. SM also specifically induced expression of Sp110b during lytic EBV replication and in several cell types. Exogenous expression of Sp110b synergistically enhanced SM-mediated accumulation of intronless and lytic viral transcripts. This synergistic effect was shown to be promoter independent, posttranscriptional, and the result of increased stabilization of target transcripts. Finally, inhibiting Sp110b expression decreased accumulation of an SM-responsive lytic EBV transcript in EBV-infected cells. These findings imply that SM induces Sp110b expression, binds to Sp110b, and utilizes the recruited Sp110b protein to increase the stability of lytic EBV transcripts, indicating that Sp110b is a component of the cellular machinery that EBV utilizes to enhance lytic EBV replication.
Global Host Immune Response: Pathogenesis and Transcriptional Profiling of Type A Influenza Viruses Expressing the Hemagglutinin and Neuraminidase Genes from the 1918 Pandemic Virus
Authors: Kash John C. , Basler Christopher F. , García-Sastre Adolfo , Carter Victoria , Billharz Rosalind , Swayne David E. , Przygodzki Ronald M. , Taubenberger Jeffery K. , Katze Michael G. , Tumpey Terrence M. 
Published: August 2004

ABSTRACTTo understand more fully the molecular events associated with highly virulent or attenuated influenza virus infections, we have studied the effects of expression of the 1918 hemagglutinin (HA) and neuraminidase (NA) genes during viral infection in mice under biosafety level 3 (agricultural) conditions. Using histopathology and cDNA microarrays, we examined the consequences of expression of the HA and NA genes of the 1918 pandemic virus in a recombinant influenza A/WSN/33 virus compared to parental A/WSN/33 virus and to an attenuated virus expressing the HA and NA genes from A/New Caledonia/20/99. The 1918 HA/NA:WSN and WSN recombinant viruses were highly lethal for mice and displayed severe lung pathology in comparison to the nonlethal New Caledonia HA/NA:WSN recombinant virus. Expression microarray analysis performed on lung tissues isolated from the infected animals showed activation of many genes involved in the inflammatory response, including cytokine, apoptosis, and lymphocyte genes that were common to all three infection groups. However, consistent with the histopathology studies, the WSN and 1918 HA/NA:WSN recombinant viruses showed increased up-regulation of genes associated with activated T cells and macrophages, as well as genes involved in apoptosis, tissue injury, and oxidative damage that were not observed in the New Caledonia HA/NA:WSN recombinant virus-infected mice. These studies document clear differences in gene expression profiles that were correlated with pulmonary disease pathology induced by virulent and attenuated influenza virus infections.
Human Immunodeficiency Virus Type 1 Matrix Inhibits and Confers Cooperativity on Gag Precursor-Membrane Interactions
Authors: Perez-Caballero David , Hatziioannou Theodora , Martin-Serrano Juan , Bieniasz Paul D. 
Published: August 2004

ABSTRACT
Human immunodeficiency virus type 1 (HIV-1) Gag multimerization and membrane binding are required for particle formation. However, it is unclear what constitutes a minimal plasma membrane-specific targeting signal and what role the matrix (MA) globular head and other Gag domains play in membrane targeting. Here, we use membrane flotation and microscopic analysis of Gag deletion mutants to demonstrate that the HIV-1 MA globular head inhibits a plasma membrane-specific targeting signal contained within the six amino-terminal MA residues. MA-mediated inhibition is relieved by concentration-dependent Gag multimerization and imparts a high degree of cooperativity on Gag-membrane association. This cooperativity may confer temporal and spatial regulation on HIV-1 assembly.
The Central Half of Pit2 Is Not Required for Its Function as a Retroviral Receptor
Authors: Bøttger Pernille , Pedersen Lene 
Published: August 2004

ABSTRACT

The type III sodium-dependent phosphate (NaP
i
) cotransporter, Pit2, is a receptor for amphotropic murine leukemia virus (A-MuLV) and 10A1 MuLV. In order to determine what is sufficient for Pit2 receptor function, a deletion mutant lacking about the middle half of the protein was made. The mutant supported entry for both viruses, unequivocally narrowing down the identification of the sequence that is sufficient to specify the receptor functions of Pit2 to its N-terminal 182 amino acids and C-terminal 170 amino acids.
Mobility of the Human Immunodeficiency Virus (HIV) Receptor CD4 and Coreceptor CCR5 in Living Cells: Implications for HIV Fusion and Entry Events
Authors: Steffens Carolyn M. , Hope Thomas J. 
Published: August 2004

ABSTRACT
The sequence of events leading to human immunodeficiency virus fusion and entry likely involves the recruitment of multiple receptor and coreceptor proteins to a specific complex by the viral envelope. Using fluorescence recovery after photobleaching technology, we find that both CD4 and CCR5 are mobile in the cell membrane. Interestingly, our findings also suggest that the seven-span transmembrane coreceptor is significantly more mobile than CD4 and requires membrane cholesterol for mobility.
Injecting drug use in Brighton, Liverpool, and London: best estimates of prevalence and coverage of public health indicators
Authors: Hickman Matthew , Higgins Vanessa , Hope Vivian , Bellis Mark , Tilling Kate , Walker Angeline , Henry John 
Published: August 2004

Study objective:To estimate the prevalence of injecting drug use (IDU) in three cities in England and to measure the coverage of key public health indicators.Design:Capture-recapture techniques with covariate effects.Setting:Liverpool, Brighton, and 12 London boroughs, 2000/01.Participants:IDU collated and matched across five data sources—community recruited survey, specialist drug treatment, arrest referral, syringe exchange, and accident and emergency—896 in Brighton, 1224 in Liverpool, and 6111 in London.Main results:It is estimated that in 2000/01 the number and prevalence of IDU aged 15–44 was 2300 (95%CI 1500 to 3700) and 2.0% (95%CI% 1.3% to 3.2%) in Brighton; 2900 (95%CI 2500 to 5000) and 1.5% (95%CI 1.3% to 2.6%) in Liverpool; 16 700 (95%CI 13 800 to 21 600) and 1.2% (95%CI 1.0% to 1.6%) in 12 London boroughs; with a prevalence of 1.7% (95%CI 1.2% to 3.3%) in inner London. It is estimated that: less than one in four IDU are in treatment in the three areas; syringe exchange programmes covered about 25% of injections in Brighton and Liverpool and 20% in London; and that the annual opioid mortality rate among IDU was 2% in Brighton compared with less than 1% in Liverpool and London.Conclusions:Credible estimates of the prevalence of injecting drug use (and key public health indicators) can be determined using covariate capture-recapture techniques. These suggest that: targets to double the number in treatment are possible: syringe distribution should be increased; and further attention, especially in Brighton, given to reducing overdose mortality.
"No Peace" in a Book of Consolation. a Framework for the Book of Isaiah?
Authors: Olley John 
Published: August 2004

AbstractAfter an overview of interpretations of the twofold statement of Isa. xlviii 22 and lvii 21 and the concluding lxvi 24 and of evidence from texts and versions, examination of vocabulary provides a basis for considering relationship to the verses' contexts and to the structure and interpretation of Isaiah. Both xlviii 22 and lvii 21 are appropriate to their literary contexts, providing cohesion and flow, and predating the framing provided by chs. i and lxv-lxvi. Irrespective of whether the verses are intended to divide xl-lxvi, the reader sees links and so is drawn to look at the blocks. lxvi 24 forms an inclusio with i 2 for the book as a whole: there is comfort and hope for "rebels", but finally warning to those who persist in rebellion.
A Study of the Elderly People Living in Nursing Homes in Iran with a Specific Focus on Tehran
Authors: Sheykhi Mohammad Taghi 
Published: August 2004

AbstractIn the present research the author has tried to bring together the literature and collected data to examine elderly people's quality of life in Iran. In the exploratory phase, a focused group of elderly people was approached and observed. The paper also is intended for students of social policy and those responsible for the elderly people. The author hopes that the present research would act as a beginning step to expand gerontology, which is less developed in countries like Iran, as a new academic discipline. Older people are particularly interesting to study, not only because they are builders of our past, and what has led to the present, but also more importantly, they constitute the group to which, in due course, most of us will belong.This paper examines the living conditions of the elderly residing at the elderly centers in Iran with special reference to Tehran through an empirical method. In this research, while reviewing the relevant literature, the author has referred to various theories as required to assess the elderly people's quality of life. The paper also explores a perspective of the elderly people in Tehran so far as their needs, expectations, their retirement life, and their health weaknesses are concerned. The survey is carried out in the hope of creating further research drives and incentives among the young social researchers.However, as the number of elderly people is on the rise in Iran due to change in the entire social structure of the country and increase in life expectancy, there is a need for further investments to prevent the likely future challenges.
Outcomes after alemtuzumab-containing reduced-intensity allogeneic transplantation regimen for relapsed and refractory non-Hodgkin lymphoma
Authors: Morris Emma , Thomson Kirsty , Craddock Charles , Mahendra Prem , Milligan Donald , Cook Gordon , Smith Graeme Murray , Parker Anne , Schey Steve , Chopra Rajesh , Hatton Christopher , Tighe Jane , Hunter Anne , Peggs Karl , Linch David , Goldstone Anthony , Mackinnon Stephen 
Published: August 2004

Abstract
We report the outcomes after reduced-intensity conditioning allogeneic stem cell transplantation (RIT) for non-Hodgkin lymphoma (NHL) in 88 patients (low-grade NHL [LG-NHL], n = 41; high-grade NHL [HG-NHL], n = 37; mantle cell lymphoma [MCL], n = 10). Thirty-seven patients had previously received autografts, and 21 were in complete remission (CR) at transplantation. Conditioning therapy consisted of alemtuzumab, fludarabine, and melphalan. Sixty-five patients received peripheral blood stem cells (PBSCs) from HLA-identical siblings, and 23 received bone marrow (BM) from matched unrelated donors. Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporin A. Grade III-IV acute GVHD developed in 4 patients, and chronic GVHD developed in 6 patients. With a median follow-up of 36 months (range, 18-60 months), the actuarial overall survival (OS) rates at 3 years were 34% for HG-NHL, 60% for MCL, and 73% for LG-NHL (P &lt; .001). The 100-day and 3-year transplant-related mortality (TRM) rates for patients with LG-NHL were 2% and 11%, respectively, and were better (P = .01) than they were for patients with HG-NHL (27% and 38%, respectively). The actuarial current progression-free survival (PFS) rate at 3 years, including the rate for patients who achieved remission after donor lymphocyte infusion (DLI) for progression, was 65% for LG-NHL, 50% for MCL, and 34% for HG-NHL (P = .002). Twenty-one patients underwent DLI for matched related donor (MD)-persistent disease or relapse, and 15 underwent DLI for mixed hematopoietic chimerism. Patients who experienced relapses of LG-NHL and chronic lymphocytic leukemia (CLL) achieved excellent PFS with extremely low TRM and GVHD, even when matched related donors were unavailable. (Blood. 2004;104:3865-3871)
In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model
Authors: Frost Patrick , Moatamed Farhad , Hoang Bao , Shi Yijiang , Gera Joseph , Yan Huajun , Frost Philip , Gibbons Jay , Lichtenstein Alan 
Published: August 2004

Abstract
In vitro studies indicate the therapeutic potential of mTOR inhibitors in treating multiple myeloma. To provide further support for this potential, we used the rapamycin analog CCI-779 in a myeloma xenograft model. CCI-779, given as 10 intraperitoneal injections, induced significant dose-dependent, antitumor responses against subcutaneous growth of 8226, OPM-2, and U266 cell lines. Effective doses of CCI-779 were associated with modest toxicity, inducing only transient thrombocytopenia and leukopenia. Immunohistochemical studies demonstrated the antitumor responses were associated with inhibited proliferation and angiogenesis, induction of apoptosis, and reduction in tumor cell size. Although CCI-779-mediated inhibition of the p70 mTOR substrate was equal in 8226 and OPM-2 tumor nodules, OPM-2 tumor growth was considerably more sensitive to inhibition of proliferation, angiogenesis, and induction of apoptosis. Furthermore, the OPM-2 tumors from treated mice were more likely to show down-regulated expression of cyclin D1 and c-myc and up-regulated p27 expression. Because earlier work suggested heightened AKT activity in OPM-2 tumors might induce hypersensitivity to mTOR inhibition, we directly tested this by stably transfecting a constitutively active AKT allele into U266 cells. The in vivo growth of the latter cells was remarkably more sensitive to CCI-779 than the growth of control U266 cells.
The γ-carboxyglutamic acid domain of anticoagulant protein S is involved in activated protein C cofactor activity, independently of phospholipid binding
Authors: Saller François , Villoutreix Bruno O. , Amelot Aymeric , Kaabache Tahar , Le Bonniec Bernard F. , Aiach Martine , Gandrille Sophie , Borgel Delphine 
Published: August 2004

AbstractWe expressed 2 chimeras between human protein S (PS) and human prothrombin (FII) in which the prothrombin γ-carboxyglutamic acid (Gla) domain replaced the PS Gla domain in native PS (GlaFII-PS) or in PS deleted of the thrombin-sensitive region (TSR) (GlaFII-ΔTSR-PS). Neither PS/FII chimera had activated protein C (APC) cofactor activity in plasma clotting assays or purified systems, but both bound efficiently to phospholipids. This pointed to a direct involvement of the PS Gla domain in APC cofactor activity through molecular interaction with APC. Using computational methods, we identified 2 opposite faces of solvent-exposed residues on the PS Gla domain (designated faces 1 and 2) as potentially involved in this interaction. Their importance was supported by functional characterization of a PS mutant in which the face 1 and face 2 PS residues were reintroduced into GlaFII-PS, leading to significant APC cofactor activity, likely through restored interaction with APC. Furthermore, by characterizing PS mutants in which PS face 1 and PS face 2 were individually replaced by the corresponding prothrombin faces, we found that face 1 was necessary for efficient phospholipid binding but that face 2 residues were not strictly required for phospholipid binding and were involved in the interaction with APC.
Evaluation of the suitability of free-energy minimization using nearest-neighbor energy parameters for RNA secondary structure prediction
Authors: Doshi Kishore J , Cannone Jamie J , Cobaugh Christian W , Gutell Robin R 
Published: August 2004

Abstract
Background
A detailed understanding of an RNA's correct secondary and tertiary structure is crucial to understanding its function and mechanism in the cell. Free energy minimization with energy parameters based on the nearest-neighbor model and comparative analysis are the primary methods for predicting an RNA's secondary structure from its sequence. Version 3.1 of Mfold has been available since 1999. This version contains an expanded sequence dependence of energy parameters and the ability to incorporate coaxial stacking into free energy calculations. We test Mfold 3.1 by performing the largest and most phylogenetically diverse comparison of rRNA and tRNA structures predicted by comparative analysis and Mfold, and we use the results of our tests on 16S and 23S rRNA sequences to assess the improvement between Mfold 2.3 and Mfold 3.1.

Results
The average prediction accuracy for a 16S or 23S rRNA sequence with Mfold 3.1 is 41%, while the prediction accuracies for the majority of 16S and 23S rRNA structures tested are between 20% and 60%, with some having less than 20% prediction accuracy. The average prediction accuracy was 71% for 5S rRNA and 69% for tRNA. The majority of the 5S rRNA and tRNA sequences have prediction accuracies greater than 60%. The prediction accuracy of 16S rRNA base-pairs decreases exponentially as the number of nucleotides intervening between the 5' and 3' halves of the base-pair increases.

Conclusion
Our analysis indicates that the current set of nearest-neighbor energy parameters in conjunction with the Mfold folding algorithm are unable to consistently and reliably predict an RNA's correct secondary structure. For 16S or 23S rRNA structure prediction, Mfold 3.1 offers little improvement over Mfold 2.3. However, the nearest-neighbor energy parameters do work well for shorter RNA sequences such as tRNA or 5S rRNA, or for larger rRNAs when the contact distance between the base-pairs is less than 100 nucleotides.