bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual Role of Prostratin in Inhibition of Infection and Reactivation of Human Immunodeficiency Virus from Latency in Primary Blood Lymphocytes and Lymphoid Tissue
Authors: Biancotto Angélique , Grivel Jean-Charles , Gondois-Rey Françoise , Bettendroffer Lise , Vigne Robert , Brown Stephen , Margolis Leonid B. , Hirsch Ivan 
Published: September 2004

ABSTRACTTo design strategies to purge latent reservoirs of human immunodeficiency virus type 1 (HIV-1), we investigated mechanisms by which a non-tumor-promoting phorbol ester, prostratin, inhibits infection of CD4+T lymphocytes and at the same time reactivates virus from latency. CD4+T lymphocytes from primary blood mononuclear cells (PBMC) and in blocks of human lymphoid tissue were stimulated with prostratin and infected with HIV-1 to investigate the effects of prostratin on cellular susceptibility to the virus. The capacity of prostratin to reactivate HIV from latency was tested in CD4+T cells harboring preintegrated and integrated latent provirus. Prostratin stimulated CD4+T cells in an aberrant way. It induced expression of the activation markers CD25 and CD69 but inhibited cell cycling. HIV-1 uptake was reduced in prostratin-stimulated CD4+T PBMC and tissues in a manner consistent with a downregulation of CD4 and CXCR4 receptors in these systems. At the postentry level, prostratin inhibited completion of reverse transcription of the viral genome in lymphoid tissue. However, prostratin facilitated integration of the reverse-transcribed HIV-1 genome in nondividing CD4+T cells and facilitated expression of already integrated HIV-1, including latent forms. Thus, while stimulation with prostratin restricts susceptibility of primary resting CD4+T cells to HIV infection at the virus cell-entry level and at the reverse transcription level, it efficiently reactivates HIV-1 from pre- and postintegration latency in resting CD4+T cells.
Comprehensive Analysis of Nef Functions Selected in Simian Immunodeficiency Virus-Infected Macaques
Authors: Schindler Michael , Münch Jan , Brenner Matthias , Stahl-Hennig Christiane , Skowronski Jacek , Kirchhoff Frank 
Published: September 2004

ABSTRACT

A variety of simian immunodeficiency virus (SIVmac)
nef
mutants have been investigated to clarify which in vitro Nef functions contribute to efficient viral replication and pathogenicity in rhesus macaques. Most of these
nef
alleles, however, were only functionally characterized for their ability to down-modulate CD4 and class I major histocompatibility complex (MHC-I) cell surface expression and to enhance SIV replication and infectivity. To obtain information on the in vivo relevance of more recently established Nef functions, we examined the ability of a large panel of constructed SIVmac Nef mutants and of variants that emerged in infected macaques to down-regulate CD3, CD28, and MHC-II and to up-regulate the MHC-II-associated invariant chain (Ii). We found that all these four Nef functions were restored in SIV-infected macaques. In most cases, however, the initial mutations and the changes selected in vivo affected several in vitro Nef functions. For example, truncated Nef proteins that emerged in animals infected with SIVmac239 containing a 152-bp deletion in
nef
efficiently modulated both CD3 and Ii surface expression. Overall, our results suggest that the effect of Nef on each of the six cellular receptors investigated contributes to viral fitness in the infected host but also indicate that modulation of CD3, MHC-I, MHC-II, or Ii surface expression alone is insufficient for SIV virulence.
Activation of TBK1 and IKKε Kinases by Vesicular Stomatitis Virus Infection and the Role of Viral Ribonucleoprotein in the Development of Interferon Antiviral Immunity
Authors: tenOever Benjamin R. , Sharma Sonia , Zou Wen , Sun Qiang , Grandvaux Nathalie , Julkunen Ilkka , Hemmi Hiroaki , Yamamoto M. , Akira Shizuo , Yeh Wen-Chen , Lin Rongtuan , Hiscott John 
Published: September 2004

ABSTRACT
Mounting an immune response to a viral pathogen involves the initial recognition of viral antigens through Toll-like receptor-dependent and -independent pathways and the subsequent triggering of signal transduction cascades. Among the many cellular kinases stimulated in response to virus infection, the noncanonical IKK-related kinases TBK1 and IKKε have been shown to phosphorylate and activate interferon regulatory factor 3 (IRF-3) and IRF-7, leading to the production of alpha/beta interferons and the development of a cellular antiviral state. In the present study, we examine the activation of TBK1 and IKKε kinases by vesicular stomatitis virus (VSV) infection in human lung epithelial A549 cells. We demonstrate that replication-competent VSV is required to induce activation of the IKK-related kinases and provide evidence that ribonucleoprotein (RNP) complex of VSV generated intracellularly during virus replication can activate TBK1 and IKKε activity. In TBK1-deficient cells, IRF-3 and IRF-7 activation is significantly reduced, although transcriptional upregulation of IKKε following treatment with VSV, double-stranded RNA, or RNP partially compensates for the loss of TBK1. Biochemical analyses with purified TBK1 and IKKε kinases in vitro demonstrate that the two kinases exhibit similar specificities with respect to IRF-3 and IRF-7 substrates and both kinases target serine residues that are important for full transcriptional activation of IRF-3 and IRF-7. These data suggest that intracellular RNP formation contributes to the early recognition of VSV infection, activates the catalytic activity of TBK1, and induces transcriptional upregulation of IKKε in epithelial cells. Induction of IKKε potentially functions as a component of the amplification mechanism involved in the establishment of the antiviral state.
Phylogenetic Analysis of Clinical Herpes Simplex Virus Type 1 Isolates Identified Three Genetic Groups and Recombinant Viruses
Authors: Norberg Peter , Bergström Tomas , Rekabdar Elham , Lindh Magnus , Liljeqvist Jan-Åke 
Published: September 2004

ABSTRACT
Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen which establishes lifelong infections. In the present study, we determined the sequence diversity of the complete genes coding for glycoproteins G (gG), I (gI), and E (gE), comprising 2.3% of the HSV-1 genome and located within the unique short (US) region, for 28 clinical HSV-1 isolates inducing oral lesions, genital lesions, or encephalitis. Laboratory strains F and KOS321 were sequenced in parallel. Phylogenetic analysis, including analysis of laboratory strain 17 (GenBank), revealed that the sequences were separated into three genetic groups. The identification of different genogroups facilitated the detection of recombinant viruses by using specific nucleotide substitutions as recombination markers. Seven of the isolates and strain 17 displayed sequences consistent with intergenic recombination, and at least four isolates were intragenic recombinants. The observed frequency of recombination based on an analysis of a short stretch of the US region suggests that most full-length HSV-1 genomes consist of a mosaic of segments from different genetic groups. Polymorphic tandem repeat regions, consisting of two to eight blocks of 21 nucleotides in the gI gene and seven to eight repeats of 3 nucleotides in the gG gene, were also detected. Laboratory strain KOS321 displayed a frameshift mutation in the gI gene with a subsequent alteration of the deduced intracellular portion of the protein. The presence of polymorphic tandem repeat regions and the different genogroup identities can be used for molecular epidemiology studies and for further detection of recombination in the HSV-1 genome.
Chorea and related disorders
Authors: Bhidayasiri R , Truong D D 
Published: September 2004

Abstract
Chorea refers to irregular, flowing, non-stereotyped, random, involuntary movements that often possess a writhing quality referred to as choreoathetosis. When mild, chorea can be difficult to differentiate from restlessness. When chorea is proximal and of large amplitude, it is called ballism. Chorea is usually worsened by anxiety and stress and subsides during sleep. Most patients attempt to disguise chorea by incorporating it into a purposeful activity. Whereas ballism is most often encountered as hemiballism due to contralateral structural lesions of the subthalamic nucleus and/or its afferent or efferent projections, chorea may be the expression of a wide range of disorders, including metabolic, infectious, inflammatory, vascular, and neurodegenerative, as well as drug induced syndromes. In clinical practice, Sydenham’s chorea is the most common form of childhood chorea, whereas Huntington’s disease and drug induced chorea account for the majority of adult onset cases. The aim of this review is to provide an up to date discussion of this disorder, as well as a practical approach to its management.
Modulation of cord blood CD8+ T-cell effector differentiation by TGF-β1 and 4-1BB costimulation
Authors: Kim Young-June , Stringfield Teresa M. , Chen Yan , Broxmeyer Hal E. 
Published: September 2004

AbstractTransforming growth factor-β1 (TGF-β1), an immunosuppressive cytokine, inhibits cytotoxic T cell (CTL) immune responses. In contrast, 4-1BB (CD137), a costimulatory molecule in the tumor necrosis factor (TNF) receptor family, amplifies CTL-mediated antitumor immune responses. We investigated whether TGF-β1 responses could be reversed by 4-1BB costimulation during in vitro differentiation of naive CD8+ T cells into effector CTL cells. TGF-β1 potently suppressed CTL differentiation of human cord blood naive CD8+ T cells as determined by reduced induction of characteristic phenotypes of effector cells and cytotoxic activity. TGF-β1-mediated suppression of CTL differentiation was abrogated by 4-1BB costimulation but not by CD28 or another member in the TNF receptor family, CD30. 4-1BB costimulation suppressed Smad2 phosphorylation induced by TGF-β1, suggesting that 4-1BB effects were at the level of TGF-β1 signaling. 4-1BB effects on the TGF-β1-mediated suppression were enhanced by interleukin 12 (IL-12) but counteracted by IL-4; 4-1BB expression was up- or down-regulated, respectively, by IL-12 and IL-4. IL-4 was more dominant than IL-12 when both cytokines were present during 4-1BB costimulation in the presence of TGF-β1. This indicates critical roles for IL-4 and IL-12 in regulating 4-1BB effects on TGF-β1-mediated suppression. (Blood. 2005;105:274-281)
The Jab1/COP9 signalosome subcomplex is a downstream mediator of Bcr-Abl kinase activity and facilitates cell-cycle progression
Authors: Tomoda Kiichiro , Kato Jun-ya , Tatsumi Eiji , Takahashi Takayuki , Matsuo Yoshinobu , Yoneda-Kato Noriko 
Published: September 2004

AbstractJab1 is a multifunctional protein associated with the signaling pathway, cell-cycle regulation, and development, and acts as a key subunit of COP9 signalosome (CSN). Jab1 promotes degradation of the cyclin-dependent kinase inhibitor p27Kip1 by transportation from the nucleus to the cytoplasm. However, there has been no clear evidence for whether and how Jab1 contributes to malignant transformation in human cancers. Here we show that Bcr-Abl tyrosine kinase facilitates the down-regulation of p27 by modulating complex formation of Jab1/CSN through the mitogen-activated protein (MAP) kinase and phosphatidylinositol 3 (PI3) kinase signaling pathways. Nearly half of the chronic myelogenous leukemia cell lines and the murine hematopoietic precursor cells expressing Bcr-Abl exhibited a marked increase in the small loose Jab1 complex located in the cytoplasm. Inhibition of Bcr-Abl kinase by STI571 induced G1 arrest and caused a recovery of the p27 level with reduction of the small Jab1 complex from the cytoplasm. Either blockade of the MAP kinase and PI3 kinase pathways by specific inhibitors or Jab1 knockdown by small interfering RNA (siRNA) prevented p27 down-regulation as well as formation of the small complex. Thus, regulation of p27 via modulation of the Jab1 subcomplex is a novel mechanism whereby Bcr-Abl oncogenic signals accelerate abnormal cell proliferation.
Atomization characteristics and prediction accuracies of hybrid break-up models for a gasoline direct injection spray
Authors: Lee Chang Sik , Kim Hyung Jun , Park Sung Wook 
Published: September 2004

The purpose of this study is to investigate the prediction accuracy of hybrid models on the atomization processes of fuel sprays injected from a gasoline direct injection system. In order to analyze the prediction characteristics of hybrid schemes, various hybrid models for the primary and secondary break-ups of high-pressure gasoline spray are formulated by combining two different models. For the primary break-up, the LISA and WAVE break-up models are used, whereas the TAB, DDB, and RT models are utilized for the secondary break-up, considering the break-up mechanism of each break-up model. Therefore, six hybrid models are applied to the simulation of the atomization process and the prediction accuracies of the break-up processes are evaluated by comparing them with the experimental results. To obtain experimental results for comparison with the predicted ones, the local Sauter mean diameter and axial mean velocity are measured by using a phase Doppler particle analyzer. Also, the spray visualization system is utilized to analyze the process of spray development and spray-tip penetration. It is revealed that all hybrid models show reasonable agreement with the experimental results of spray-tip penetration. On the other hand, different accuracies are shown in the distributions of local SMD and axial mean velocity.
A Lagrangian trajectory filter for constituent data assimilation
Authors: Lyster Peter M. , Cohn Stephen E. , Zhang Banglin , Chang Lang‐Ping , Ménard Richard , Olson Kevin , Renka Robert 
Published: September 2004

AbstractWe have developed a new numerical algorithm, the Lagrangian filter, for solving the Kalman filter equations for assimilation of constituent observations directly on trajectories that propagate with the flow. This is a finite‐dimensional approximation of the solution of the state estimation problem by characteristics, and may be thought of as an extension of methods such as trajectory mapping. The Lagrangian filter provides a natural framework for the study and solution of the constituent data assimilation problem because of the conservative properties of the state and its estimation‐error variance and covariance along trajectories. Considerable insight into the behaviour of the filter is gained as a result of these properties. The Lagrangian filter also requires significantly fewer floating point operations than the Eulerian Kalman filter because of its simple error covariance propagation step. We implemented it for two‐dimensional flow on isentropes in the stratosphere and assimilated methane observations from the Upper Atmosphere Research Satellite. Results are validated against those of the Eulerian filter. Copyright © 2004 Royal Meteorological Society
North Atlantic forcing of climate and its uncertainty from a multi‐model experiment
Authors: Rodwell M. J. , Drévillon M. , Frankignoul C. , Hurrell J. W. , Pohlmann H. , Stendel M. , Sutton R. T. 
Published: September 2004

AbstractTo understand recent climate change in the North Atlantic region and to produce better climate forecasts with uncertainty estimates it is important to determine the atmospheric ‘response’ to Atlantic sea‐surface temperature (SST) forcing. There have been conflicting results regarding the strength, character and tropical‐versus‐extratropical origin of this response. For model‐based studies, this may indicate differing sensitivities to Atlantic SST, but the comparison is complicated by changes in experimental design. Here, a highly controlled experiment with five atmospheric models is undertaken. The influence of realistic (if reasonably strong) and optimally chosen North Atlantic (equator to 70°N) SST anomalies is isolated. Unexpected global agreement between the models is found (e.g. the North Atlantic Oscillation (NAO), Eurasian temperatures, rainfall over the Americas and Africa, and the Asian monsoon). The extratropical North Atlantic region response appears to be associated with remote Caribbean and tropical Atlantic SST anomalies, and with local forcing. Some features such as the European winter‐temperature response would be stronger than atmospheric ‘noise’ if the prescribed SST anomalies persisted for just two years. More generally, Atlantic air–sea interaction appears to be important for climate variability on the 30‐year timescale and, thus, to be important in the climate‐change context. The multi‐model mean response patterns are in reasonable agreement with observational estimates, although the model response magnitudes may be too weak. The similarity between their responses helps to reconcile models. Inter‐model differences do still exist and these are discussed and quantified. © Crown copyright, 2004.
Diagnostics of linear and incremental approximations in 4D‐Var
Authors: Tr'emolet Yannick 
Published: September 2004

AbstractThe validity of the tangent linear approximation and of the incremental 4D‐Var formulation is evaluated in the operational context. In ECMWF's operational system, the linear and adjoint models are run at a lower resolution than the nonlinear model. Furthermore, the physics are simpler in the tangent linear and adjoint than in the nonlinear model. Comparisons are made between the output of the linear model and the finite difference obtained by running the nonlinear model twice, with and without adding the analysis increment. The accuracy of the linear model is assessed with respect to resolution, linearized physics and the length of the assimilation window.The most striking results are that linearization errors are larger than expected and that large errors appear very early in the assimilation window. It is also shown that higher resolution 4D‐Var will require more accurate linear physics than currently available. A modification of the computation of the trajectory around which the problem is linearized is shown to improve the accuracy of the linearization.The results and diagnostic tools presented should provide guidance for further developments of the incremental 4D‐Var, with respect to resolution changes and improvements in linearized physics and dynamics. Copyright © 2004 Royal Meteorological Society
The effect of raindrop clustering on collision‐induced break‐up of raindrops
Authors: McFarquhar Greg M. 
Published: September 2004

AbstractThe impact of raindrop clustering on raindrop mean free paths, mean times between raindrop collisions, and raindrop collision rates is examined using prior observations of raindrop pair cross‐correlation functions and raindrop size distributions (RSDs). Variations in observed RSDs cause collision rates to vary by more than a factor of 2.5 for identical rain rates; effects due to raindrop clustering also increase collision rates by 2.5 times or more. High uncertainty in the factor of 2.5 and its variability exists because observations of raindrop inter arrival times, upon which observations of clustering are based, are relatively rare. Clustering increases collision rates because large raindrops in preferred or clustered regions overtake smaller drops in the same regions. The form of the RSD has a significant impact on the collision frequency because the spread in raindrop fall speeds, and hence the ability of large drops to overtake small ones, depends highly on the RSD.Depending on the form of the RSD that develops at precipitation onset, numerical models suggest that there can be sufficient raindrop interactions to approach equilibrium distributions generated from the opposing forces of coalescence and break‐up for rain rates higher than about 50 mm h−1. However, equilibrium distributions do not occur in nature, most likely because the large spread in fragment size distributions generated for a specific pair of colliding raindrops causes substantial local variations in RSDs. Significant sampling times under conditions of heavy rain would be required to return to the form of an equilibrium distribution from statistical effects alone, if it indeed existed. Copyright © 2004 Royal Meteorological Society
Evaluation of Quality-Control Criteria for Microarray Gene Expression Analysis
Authors: Dumur Catherine I , Nasim Suhail , Best Al M , Archer Kellie J , Ladd Amy C , Mas Valeria R , Wilkinson David S , Garrett Carleton T , Ferreira-Gonzalez Andrea 
Published: September 2004

Abstract
Background: Development of quality-control criteria to ensure reproducibility of microarray results for potential clinical application is still in its infancy.
Methods: In the present studies we developed quality-control criteria and evaluated their effect in microarray data analysis using total RNA from cell lines, frozen tumors, and a commercially available reference RNA. Quality-control criteria such as A260/A280 ratios, percentage of rRNA, and median size of cDNA and cRNA synthesis products were evaluated for robustness in microarray analysis. Furthermore, precision studies using a reference material were performed on the Affymetrix® HG-U133A high-density oligonucleotide microarrays. The same reference RNA sample was examined in 16 different chips run on 2 different days in the four different modules of the Affymetrix fluidics workstation. Fresh and frozen fragmented cRNAs were also compared. An ANOVA model was fit to identify the main sources of variation.
Results: Good-quality samples showed &gt;30% rRNA in the electropherograms and cDNA and cRNA synthesis products with median sizes of 2.0 and 3.0 kb, respectively. Precision studies showed that the main source of variation was the day-to-day variability, minimally affecting hybridization exogenous control genes. Altogether, the results showed that the Affymetrix Genechip® system is highly reproducible when RNA that meet the quality-control criteria are used (overall P &gt;0.01).
Conclusions: These results confirm the need to establish defined quality-control criteria for sample quality to distinguish between analytical and biological variability.
Reverse Transcription-Multiplex PCR Assay for Simultaneous Detection of Escherichia coli O157:H7, Vibrio cholerae O1, and Salmonella Typhi
Authors: Morin Nicole J , Gong Zhilong , Li Xing-Fang 
Published: September 2004

Abstract
Background: Escherichia coli O157:H7, Vibrio cholerae O1, and Salmonella Typhi are pathogenic bacteria that can be found in contaminated water supplies throughout the world. No currently available assays can simultaneously detect and identify all three pathogens. Our aim was to develop a rapid and reliable technique for simultaneous detection of these pathogens.
Methods: Four unique genes were chosen as the targets of detection. Forward and reverse primers were designed to specifically amplify different sizes of these target genes: a 239-bp region of the E. coli O157 lipopolysaccharide (LPS) gene (rfbE); a 179-bp region of the H7 flagellin gene (fliC); a 419-bp region of the V. cholerae O1 LPS gene (rfbE); and a 329-bp region of Salmonella Typhi LPS gene (tyv). To ensure the detection of only viable replicating bacteria, RNA was extracted for analysis. After reverse transcription, cDNAs were simultaneously amplified in a single tube by multiplex PCR. The multiplex PCR products were analyzed by gel electrophoresis. To characterize the assay we analyzed, in a blinded fashion, seven unknown RNA samples containing various combinations of total RNA from these bacteria as well as clinical isolates.
Results: All seven unknown RNA samples were correctly identified. The assay was able to detect and identify as few as 30 cells of E. coli O157:H7 and Salmonella Typhi in clinical isolates, and the presence of other bacteria did not interfere with the analysis.
Conclusion: An assay combining reverse transcription with single-tube multiplex PCR was successfully developed and validated for simultaneous detection of viable E. coli O157:H7, V. cholerae O1, and Salmonella Typhi.