bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuraminidase Inhibitor-Resistant and -Sensitive Influenza B Viruses Isolated from an Untreated Human Patient
Authors: Hurt Aeron C. , Iannello Pina , Jachno Kim , Komadina Naomi , Hampson Alan W. , Barr Ian G. , McKimm-Breschkin Jennifer L. 
Published: April 2006

ABSTRACT
An influenza B virus from an infant with no history of treatment or contact with neuraminidase inhibitors demonstrated a significant reduction in sensitivity to these drugs. Here, we describe the analysis of a mixed viral population that contained a novel D197E amino acid substitution that was responsible for this reduction.
Effects of Mutations in the Human Immunodeficiency Virus Type 1
gag
Gene on RNA Packaging and Recombination
Authors: Nikolaitchik Olga , Rhodes Terence D. , Ott David , Hu Wei-Shau 
Published: April 2006

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) recombination occurs during reverse transcription when parts of the two copackaged RNAs are used as templates for DNA synthesis. It was previously hypothesized that HIV-1 Gag polyproteins preferentially encapsidate the RNA from which they were translated (
cis
-packaging hypothesis). This hypothesis implies that mutants encoding Gag that cannot efficiently package viral RNA are selected against at two levels: these mutants do not generate infectious virus, and these mutants are not efficiently rescued by the wild-type virus because the mutant RNAs are packaged at much lower levels than are those of the wild-type genome. Therefore, genetic information encoded by
gag
mutants can be rapidly lost in the viral population. To test this prediction of the
cis
-packaging hypothesis, we examined several
gag
mutants by measuring the efficiencies of the mutant RNAs in being packaged in
trans
in the presence of wild-type virus and determining the rates of recombination between
gag
mutants and wild-type viruses. We observed that the viral RNAs from the nucleocapsid zinc finger or the capsid truncation mutant were packaged efficiently in
trans
, and these mutant viruses also frequently recombined with the wild-type viruses. In contrast, viral RNAs from mutants containing a 6-nucleotide substitution encompassing the
gag
AUG were not efficiently encapsidated, resulting in a low rate of recombination between the mutants and wild-type viruses. Further analyses revealed that other, more subtle mutations changing the
gag
AUG and abolishing Gag translation did not interfere with efficient encapsidation of the mutant RNA. Our results indicated that neither the
gag
AUG sequence nor Gag translation is essential for viral RNA encapsidation, and Gag can package both wild-type and
gag
mutant RNAs with similar efficiencies. Therefore, we propose that HIV-1 RNA encapsidation occurs mainly in
trans
, and most
gag
mutants can be rescued by wild-type virus; therefore, they are unlikely to face the aforementioned double-negative selection.
A Reliable Phenotype Predictor for Human Immunodeficiency Virus Type 1 Subtype C Based on Envelope V3 Sequences
Authors: Jensen Mark A. , Coetzer Mia , van 't Wout Angélique B. , Morris Lynn , Mullins James I. 
Published: April 2006

ABSTRACT

In human immunodeficiency virus type 1 (HIV-1) subtype B infections, the emergence of viruses able to use CXCR4 as a coreceptor is well documented and associated with accelerated CD4 decline and disease progression. However, in HIV-1 subtype C infections, responsible for more than 50% of global infections, CXCR4 usage is less common, even in individuals with advanced disease. A reliable phenotype prediction method based on genetic sequence analysis could provide a rapid and less expensive approach to identify possible CXCR4 variants and thus increase our understanding of subtype C coreceptor usage. For subtype B V3 loop sequences, genotypic predictors have been developed based on position-specific scoring matrices (PSSM). In this study, we apply this methodology to a training set of 279 subtype C sequences of known phenotypes (228 non-syncytium-inducing [NSI] CCR5
+
and 51 SI CXCR4
+
sequences) to derive a C-PSSM predictor. Specificity and sensitivity distributions were estimated by combining data set bootstrapping with leave-one-out cross-validation, with random sampling of single sequences from individuals on each bootstrap iteration. The C-PSSM had an estimated specificity of 94% (confidence interval [CI], 92% to 96%) and a sensitivity of 75% (CI, 68% to 82%), which is significantly more sensitive than predictions based on other methods, including a commonly used method based on the presence of positively charged residues (sensitivity, 47.8%). A specificity of 83% and a sensitivity of 83% were achieved with a validation set of 24 SI and 47 NSI unique subtype C sequences. The C-PSSM performs as well on subtype C V3 loops as existing subtype B-specific methods do on subtype B V3 loops. We present bioinformatic evidence that particular sites may influence coreceptor usage differently, depending on the subtype.
African Swine Fever Virus Protein pE296R Is a DNA Repair Apurinic/Apyrimidinic Endonuclease Required for Virus Growth in Swine Macrophages
Authors: Redrejo-Rodríguez Modesto , García-Escudero Ramón , Yáñez-Muñoz Rafael J. , Salas María L. , Salas José 
Published: April 2006

ABSTRACT

We show here that the African swine fever virus (ASFV) protein pE296R, predicted to be a class II apurinic/apyrimidinic (AP) endonuclease, possesses endonucleolytic activity specific for AP sites. Biochemical characterization of the purified recombinant enzyme indicated that the

K
m

and catalytic efficiency values for the endonucleolytic reaction are in the range of those reported for
Escherichia coli
endonuclease IV (endo IV) and human Ape1. In addition to endonuclease activity, the ASFV enzyme has a proofreading 3′→5′ exonuclease activity that is considerably more efficient in the elimination of a mismatch than in that of a correctly paired base. The three-dimensional structure predicted for the pE296R protein underscores the structural similarities between endo IV and the viral protein, supporting a common mechanism for the cleavage reaction. During infection, the protein is expressed at early times and accumulates at later times. The early enzyme is localized in the nucleus and the cytoplasm, while the late protein is found only in the cytoplasm. ASFV carries two other proteins, DNA polymerase X and ligase, that, together with the viral AP endonuclease, could act as a viral base excision repair system to protect the virus genome in the highly oxidative environment of the swine macrophage, the virus host cell. Using an ASFV deletion mutant lacking the E296R gene, we have determined that the viral endonuclease is required for virus growth in macrophages but not in Vero cells. This finding supports the existence of a viral reparative system to maintain virus viability in the infected macrophage.
The High-Frequency Major Histocompatibility Complex Class I Allele
Mamu-B

*

17
Is Associated with Control of Simian Immunodeficiency Virus SIVmac239 Replication
Authors: Yant Levi J. , Friedrich Thomas C. , Johnson Randall C. , May Gemma E. , Maness Nicholas J. , Enz Alissa M. , Lifson Jeffrey D. , O'Connor David H. , Carrington Mary , Watkins David I. 
Published: April 2006

ABSTRACT

Particular HLA alleles are associated with reduced human immunodeficiency virus replication. It has been difficult, however, to characterize the immune correlates of viral control. An analysis of the influence of major histocompatibility complex class I alleles on viral control in 181 simian immunodeficiency virus SIVmac239-infected rhesus macaques revealed that
Mamu-B

*

17
was associated with a 26-fold reduction in plasma virus concentrations (
P
< 0.001).
Mamu-B

*

17
was also enriched 1,000-fold in a group of animals that controlled viral replication. Even after accounting for this group,
Mamu-B

*

17
was associated with an eightfold reduction in plasma virus concentrations (
P
< 0.001).
Mamu-B

*

17-
positive macaques could, therefore, facilitate our understanding of the correlates of viral control.
Rainfall Climate Regimes: The Relationship of Regional TRMM Rainfall Biases to the Environment
Authors: Berg Wesley , L'Ecuyer Tristan , Kummerow Christian 
Published: April 2006

Abstract
Intercomparisons of satellite rainfall products have historically focused on the issue of global mean biases. Regional and temporal variations in these biases, however, are equally important for many climate applications. This has led to a critical examination of rainfall estimates from the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) and precipitation radar (PR). Because of the time-dependent nature of these biases, it is not possible to apply corrections based on regionally defined characteristics. Instead, this paper seeks to relate PR–TMI differences to physical variables that can lead to a better understanding of the mechanisms responsible for the observed differences. To simplify the analysis, issues related to differences in rainfall detection and intensity are investigated separately. For clouds identified as raining by both sensors, differences in rainfall intensity are found to be highly correlated with column water vapor. Adjusting either TMI or PR rain rates based on this simple relationship, which is relatively invariant over both seasonal and interannual time scales, results in a 65%–75% reduction in the rms difference between seasonally averaged climate rainfall estimates. Differences in rainfall detection are most prominent along the midlatitude storm tracks, where widespread, isolated convection trailing frontal systems is often detected only by the higher-resolution PR. Conversely, over the East China Sea clouds below the ∼18-dBZ PR rainfall detection threshold are frequently identified as raining by the TMI. Calculations based on in situ aerosol data collected south of Japan support a hypothesis that high concentrations of sulfate aerosols may contribute to abnormally high liquid water contents within nonprecipitating clouds in this region.
North Atlantic Subtropical Mode Waters and Ocean Memory in HadCM3
Authors: Old Chris , Haines Keith 
Published: April 2006

Abstract
A study of the formation and propagation of volume anomalies in North Atlantic Mode Waters is presented, based on 100 yr of monthly mean fields taken from the control run of the Third Hadley Centre Coupled Ocean–Atmosphere GCM (HadCM3). Analysis of the temporal and spatial variability in the thickness between pairs of isothermal surfaces bounding the central temperature of the three main North Atlantic subtropical mode waters shows that large-scale variability in formation occurs over time scales ranging from 5 to 20 yr. The largest formation anomalies are associated with a southward shift in the mixed layer isothermal distribution, possibly due to changes in the gyre dynamics and/or changes in the overlying wind field and air–sea heat fluxes. The persistence of these anomalies is shown to result from their subduction beneath the winter mixed layer base where they recirculate around the subtropical gyre in the background geostrophic flow. Anomalies in the warmest mode (18°C) formed on the western side of the basin persist for up to 5 yr. They are removed by mixing transformation to warmer classes and are returned to the seasonal mixed layer near the Gulf Stream where the stored heat may be released to the atmosphere. Anomalies in the cooler modes (16° and 14°C) formed on the eastern side of the basin persist for up to 10 yr. There is no clear evidence of significant transformation of these cooler mode anomalies to adjacent classes. It has been proposed that the eastern anomalies are removed through a tropical–subtropical water mass exchange mechanism beneath the trade wind belt (south of 20°N). The analysis shows that anomalous mode water formation plays a key role in the long-term storage of heat in the model, and that the release of heat associated with these anomalies suggests a predictable climate feedback mechanism.
Correction of a murine model of von Willebrand disease by gene transfer
Authors: Pergolizzi Robert G. , Jin Guangchun , Chan Diane , Pierre Lorraine , Bussel James , Ferris Barbara , Leopold Philip L. , Crystal Ronald G. 
Published: April 2006

Abstractvon Willebrand disease (VWD), the most common inherited bleeding disorder in the U.S. population, is caused by defects in the expression and processing of von Willebrand factor (VWF), a blood glycoprotein required for normal hemostasis that mediates the adhesion of platelets to sites of vascular damage by binding to specific platelet glycoproteins and to constituents of exposed connective tissue. To assess whether VWF deficiency can be corrected by gene transfer, a plasmid expressing the intact 8.4-kb murine VWF coding sequence, directed by the cyto-megalovirus immediate/early promoter/enhancer, was delivered through hydrodynamic tail vein injection into VWF knockout mice (VWF–/–) that exhibit defects in hemostasis, including highly prolonged bleeding time and spontaneous bleeding events, closely mimicking severe human VWD. VWF antigen levels in plasma from animals receiving VWF cDNA, but not control animals, revealed normalized levels of circulating VWF that persisted for at least 1 week after injection. Western blot analysis of plasma from animals receiving VWF cDNA, but not control animals, revealed high molecular–weight multimers with patterns similar to those observed in wild-type mice. Reverse transcription–polymerase chain reaction (RT-PCR) on RNA isolated from the livers of animals receiving VWF cDNA, but not control animals, demonstrated that VWF was expressed in the liver, and immunohistochemical analysis of the livers of treated VWF–/– mice revealed VWF-specific staining throughout the liver parenchyma but not in endothelial cells. Plasma from treated VWF–/– mice, but not control VWF–/– mice, supported the hypothesis that murine platelets aggregate in the presence of botrocetin. Although levels of circulating factor VIII in untreated VWF–/– mice were less than 10% those in wild-type mice, levels of factor VIII in VWF–/– animals treated with VWF cDNA, but not in control animals, were normalized to values in wild-type mice, indicating the restoration of factor VIII carrier function for VWF in treated mice that persisted for at least 1 week at higher doses of VWF cDNA. Most important, bleeding time was normalized by 48 hours after the delivery of VWF cDNA, but not by the control plasmid. These data suggest that with the use of gene transfer of VWF cDNA, VWF protein can be expressed, processed, and secreted in a physiologically active form; thus, it may be possible to correct VWD using gene transfer.
VEGF regulates the mobilization of VEGFR2/KDR from an intracellular endothelial storage compartment
Authors: Gampel Alexandra , Moss Lara , Jones Matt C. , Brunton Val , Norman Jim C. , Mellor Harry 
Published: April 2006

AbstractEndothelial cells respond to vascular endothelial growth factor (VEGF) to produce new blood vessels. This process of angiogenesis makes a critical contribution during embryogenesis and also in the response to ischemia in adult tissues. We have studied the intracellular trafficking of the major VEGF receptor KDR (VEGFR2). Unlike other related growth factor receptors, we find that a significant proportion of KDR is held in an endosomal storage pool within endothelial cells. We find that KDR can be delivered to the plasma membrane from this intracellular pool and that VEGF stimulates this recycling to the cell surface. KDR recycling appears to be distinct from the previously characterized Rab4- and Rab11-dependent pathways, but, instead, KDR+ recycling vesicles contain Src tyrosine kinase and VEGF-stimulated recycling requires Src activation. Taken together, these data show that intracellular trafficking of KDR is markedly different from other receptor tyrosine kinases and suggest that the regulation of KDR trafficking by VEGF provides a novel mechanism for controlling the sensitivity of endothelial cells to proangiogenic signals.
Support vector machine for classification of meiotic recombination hotspots and coldspots in Saccharomyces cerevisiae based on codon composition
Authors: Zhou Tong , Weng Jianhong , Sun Xiao , Lu Zuhong 
Published: April 2006

Abstract

Background
Meiotic double-strand breaks occur at relatively high frequencies in some genomic regions (hotspots) and relatively low frequencies in others (coldspots). Hotspots and coldspots are receiving increasing attention in research into the mechanism of meiotic recombination. However, predicting hotspots and coldspots from DNA sequence information is still a challenging task.

Results
We present a novel method for classification of hot and cold ORFs located in hotspots and coldspots respectively in Saccharomyces cerevisiae, using support vector machine (SVM), which relies on codon composition differences. This method has achieved a high classification accuracy of 85.0%. Since codon composition is a fusion of codon usage bias and amino acid composition signals, the ability of these two kinds of sequence attributes to discriminate hot ORFs from cold ORFs was also investigated separately. Our results indicate that neither codon usage bias nor amino acid composition taken separately performed as well as codon composition. Moreover, our SVM based method was applied to the full genome: We predicted the hot/cold ORFs from the yeast genome by using cutoffs of recombination rate. We found that the performance of our method for predicting cold ORFs is not as good as that for predicting hot ORFs. Besides, we also observed a considerable correlation between meiotic recombination rate and amino acid composition of certain residues, which probably reflects the structural and functional dissimilarity between the hot and cold groups.

Conclusion
We have introduced a SVM-based novel method to discriminate hot ORFs from cold ones. Applying codon composition as sequence attributes, we have achieved a high classification accuracy, which suggests that codon composition has strong potential to be used as sequence attributes in the prediction of hot and cold ORFs.
IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(D)J recombinations
Authors: Baum Thierry-Pascal , Hierle Vivien , Pasqual Nicolas , Bellahcene Fatena , Chaume Denys , Lefranc Marie-Paule , Jouvin-Marche Evelyne , Marche Patrice Noël , Demongeot Jacques 
Published: April 2006

AbstractBackgroundAdaptative immune repertoire diversity in vertebrate species is generated by recombination of variable (V), diversity (D) and joining (J) genes in the immunoglobulin (IG) loci of B lymphocytes and in the T cell receptor (TR) loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level involve recombination signal sequences (RSS). Whereas many data exist, they are scattered in non specialized resources with different nomenclatures (eg. flat files) and are difficult to extract.DescriptionIMGT/GeneInfo is an online information system that provides, through a user-friendly interface, exhaustive information resulting from the complex mechanisms of T cell receptor V-J and V-D-J recombinations. T cells comprise two populations which express the αβ and γδ TR, respectively. The first version of the system dealt with theHomo sapiensandMus musculusTRA and TRB loci whose gene rearrangements allow the synthesis of the αβ TR chains. In this paper, we present the second version of IMGT/GeneInfo where we complete the database for theHomo sapiensandMus musculusTRG and TRD loci along with the introduction of a quality control procedure for existing and new data. We also include new functionalities to the four loci analysis, giving, to date, a very informative tool which allows to work on V(D)J genes of all TR loci in both human and mouse species. IMGT/GeneInfo provides more than 59,000 rearrangement combinations with a full gene description which is freely available athttp://imgt.cines.fr/GeneInfo.ConclusionIMGT/GeneInfo allows all TR information sequences to be in the same spot, and are now available within two computer-mouse clicks. This is useful for biologists and bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and their applications in immune response analysis.
The complete chloroplast genome sequence of the chlorophycean green alga Scenedesmus obliquus reveals a compact gene organization and a biased distribution of genes on the two DNA strands
Authors: de Cambiaire Jean-Charles , Otis Christian , Lemieux Claude , Turmel Monique 
Published: April 2006

Abstract

Background
The phylum Chlorophyta contains the majority of the green algae and is divided into four classes. While the basal position of the Prasinophyceae is well established, the divergence order of the Ulvophyceae, Trebouxiophyceae and Chlorophyceae (UTC) remains uncertain. The five complete chloroplast DNA (cpDNA) sequences currently available for representatives of these classes display considerable variability in overall structure, gene content, gene density, intron content and gene order. Among these genomes, that of the chlorophycean green alga Chlamydomonas reinhardtii has retained the least ancestral features. The two single-copy regions, which are separated from one another by the large inverted repeat (IR), have similar sizes, rather than unequal sizes, and differ radically in both gene contents and gene organizations relative to the single-copy regions of prasinophyte and ulvophyte cpDNAs. To gain insights into the various changes that underwent the chloroplast genome during the evolution of chlorophycean green algae, we have sequenced the cpDNA of Scenedesmus obliquus, a member of a distinct chlorophycean lineage.

Results
The 161,452 bp IR-containing genome of Scenedesmus features single-copy regions of similar sizes, encodes 96 genes, i.e. only two additional genes (infA and rpl12) relative to its Chlamydomonas homologue and contains seven group I and two group II introns. It is clearly more compact than the four UTC algal cpDNAs that have been examined so far, displays the lowest proportion of short repeats among these algae and shows a stronger bias in clustering of genes on the same DNA strand compared to Chlamydomonas cpDNA. Like the latter genome, Scenedesmus cpDNA displays only a few ancestral gene clusters. The two chlorophycean genomes share 11 gene clusters that are not found in previously sequenced trebouxiophyte and ulvophyte cpDNAs as well as a few genes that have an unusual structure; however, their single-copy regions differ considerably in gene content.

Conclusion
Our results underscore the remarkable plasticity of the chlorophycean chloroplast genome. Owing to this plasticity, only a sketchy portrait could be drawn for the chloroplast genome of the last common ancestor of Scenedesmus and Chlamydomonas.