bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variability of Respiratory Syncytial Viruses (RSV) Prevalent in Southwestern China from 2006 to 2009: Emergence of Subgroup B and A RSV as Dominant Strains
Authors: Zhang Zhi-yong , Du Li-na , Chen Xin , Zhao Yao , Liu En-mei , Yang Xi-qiang , Zhao Xiao-dong 
Published: February 2010

ABSTRACT
Respiratory syncytial virus (RSV) is the most commonly identified viral agent in young children with acute respiratory tract infections (ARIs) and often causes repeated infections throughout life. This study investigated the genetic variability of the attachment (G) protein gene among RSV strains prevalent in southwestern China. Reverse transcription-PCR (RT-PCR) for a fragment of the RSV G gene was performed with nasopharyngeal aspirates (NPAs) collected from children with ARIs hospitalized in Chongqing Children's Hospital, Chongqing, China. A total of 1,387 NPA specimens were collected from April 2006 to March 2009, and 439 (31.7%) were positive for RSV. During the study period, subgroup A and B viruses accounted for 79.5% (349/439) and 19.8% (87/439) of the total positive samples, respectively. Both subgroup A and B viruses were identified in three samples. Subgroup A viruses were predominant during two epidemic seasons (2006 to 2008), while subgroup B strains prevailed during the 2008-2009 epidemic season. Phylogenetic analyses showed that all 30 group A strains could be clustered into one genotype, genotype GA2, and 30 group B strains could be clustered into three genotypes, genotypes GB1, GB3, and BA, among which 17 genotype BA strains were detected from 23 group B strains selected during the 2008-2009 epidemic season. The G gene of genotype BA was predicted to encode proteins of five different lengths. These data suggest that group A RSV likely predominated in southwestern China and that a new genotype of subgroup B with a 60-nucleotide insertion, named BA-like virus, became the dominant genotype in the 2008-2009 epidemic season.
Antagonism of CD317 Restriction of Human Immunodeficiency Virus Type 1 (HIV-1) Particle Release and Depletion of CD317 Are Separable Activities of HIV-1 Vpu
Authors: Goffinet Christine , Homann Stefanie , Ambiel Ina , Tibroni Nadine , Rupp Daniel , Keppler Oliver T. , Fackler Oliver T. 
Published: February 2010

ABSTRACT
Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires cellular depletion of the restriction factor is unclear. Here, we characterized CD317 variants with mutations in putative sorting or ubiquitination motifs. All mutants still potently impaired release of Vpu-defective HIV-1 and remained sensitive to Vpu-mediated release enhancement. Importantly, this virological antagonism correlated with surface downregulation of CD317 mutants by Vpu, while intracellular pools of these mutants, which were consistently depleted of the wild-type protein, were highly variable or even enhanced. Thus, Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation.
CD147/EMMPRIN Acts as a Functional Entry Receptor for Measles Virus on Epithelial Cells
Authors: Watanabe Akira , Yoneda Misako , Ikeda Fusako , Terao-Muto Yuri , Sato Hiroki , Kai Chieko 
Published: February 2010

ABSTRACT

Measles is a highly contagious human disease caused by measles virus (MeV) and remains the leading cause of death in children, particularly in developing countries. Wild-type MeV preferentially infects lymphocytes by using signaling lymphocytic activation molecule (SLAM), whose expression is restricted to hematopoietic cells, as a receptor. MeV also infects other epithelial and neuronal cells that do not express SLAM and causes pneumonia and diarrhea and, sometimes, serious symptoms such as measles encephalitis and subacute sclerosing panencephalitis. The discrepancy between the tissue tropism of MeV and the distribution of SLAM-positive cells suggests that there are unknown receptors other than SLAM for MeV. Here we identified CD147/EMMPRIN (extracellular matrix metalloproteinase inducer), a transmembrane glycoprotein, which acts as a receptor for MeV on epithelial cells. Furthermore, we found the incorporation of cyclophilin B (CypB), a cellular ligand for CD147, in MeV virions, and showed that inhibition of CypB incorporation significantly attenuated SLAM-independent infection on epithelial cells, while it had no effect on SLAM-dependent infection. To date, MeV infection was considered to be triggered by binding of its hemagglutinin (H) protein and cellular receptors. Our present study, however, indicates that MeV infection also occurs via CD147 and virion-associated CypB, independently of MeV H. Since CD147 is expressed in a variety of cells, including epithelial and neuronal cells, this molecule possibly functions as an entry receptor for MeV in SLAM-negative cells. This is the first report among members of the
Mononegavirales
that CD147 is used as a virus entry receptor via incorporated CypB in the virions.
Structure-Based Mutational Analysis of the Bovine Papillomavirus E1 Helicase Domain Identifies Residues Involved in the Nonspecific DNA Binding Activity Required for Double Trimer Formation
Authors: Liu Xiaofei , Schuck Stephen , Stenlund Arne 
Published: February 2010

ABSTRACT
The papillomavirus E1 protein is a multifunctional initiator protein responsible for preparing the viral DNA template for initiation of DNA replication. The E1 protein encodes two DNA binding activities that are required for initiation of DNA replication. A well-characterized sequence-specific DNA binding activity resides in the E1 DBD and is used to tether E1 to the papillomavirus ori. A non-sequence-specific DNA binding activity is also required for formation of the E1 double trimer (DT) complex, which is responsible for the local template melting that precedes loading of the E1 helicase. This DNA binding activity is very poorly understood. We use a structure-based mutagenesis approach to identify residues in the E1 helicase domain that are required for the non-sequence-specific DNA binding and DT formation. We found that three groups of residues are involved in nonspecific DNA binding: the E1 β-hairpin structure containing R505, K506, and H507; a hydrophobic loop containing F464; and a charged loop containing K461 together generate the binding surface involved in nonspecific DNA binding. These residues are well conserved in the T antigens from the polyomaviruses, indicating that the polyomaviruses share this nonspecific DNA binding activity.
Generation of the Pathogenic R5-Tropic Simian/Human Immunodeficiency Virus SHIV
AD8
by Serial Passaging in Rhesus Macaques
Authors: Nishimura Yoshiaki , Shingai Masashi , Willey Ronald , Sadjadpour Reza , Lee Wendy R. , Brown Charles R. , Brenchley Jason M. , Buckler-White Alicia , Petros Rahel , Eckhaus Michael , Hoffman Victoria , Igarashi Tatsuhiko , Martin Malcolm A. 
Published: February 2010

ABSTRACT

A new pathogenic R5-tropic simian/human immunodeficiency virus (SHIV) was generated following serial passaging in rhesus macaques. All 13 animals inoculated with SHIV
AD8
passaged lineages experienced marked depletions of CD4
+
T cells. Ten of these infected monkeys became normal progressors (NPs) and had gradual losses of both memory and naïve CD4
+
T lymphocytes, generated antiviral CD4
+
and CD8
+
T cell responses, and sustained chronic immune activation while maintaining variable levels of plasma viremia (10
2
to 10
5
RNA copies/ml for up to 3 years postinfection [p.i.]). To date, five NPs developed AIDS associated with opportunistic infections caused by
Pneumocystis carinii
,
Mycobacterium avium
, and
Campylobacter coli
that required euthanasia between weeks 100 and 199 p.i. Three other NPs have experienced marked depletions of circulating CD4
+
T lymphocytes (92 to 154 cells/μl) following 1 to 2 years of infection. When tested for coreceptor usage, the viruses isolated from four NPs at the time of their euthanasia remained R5 tropic. Three of the 13 SHIV
AD8
-inoculated macaques experienced a rapid-progressor syndrome characterized by sustained plasma viremia of >1 × 10
7
RNA copies/ml and rapid irreversible loss of memory CD4
+
T cells that required euthanasia between weeks 19 and 23 postinfection. The sustained viremia, associated depletion of CD4
+
T lymphocytes, and induction of AIDS make the SHIV
AD8
lineage of viruses a potentially valuable reagent for vaccine studies.
CD317/Tetherin Is Enriched in the HIV-1 Envelope and Downregulated from the Plasma Membrane upon Virus Infection
Authors: Habermann Anja , Krijnse-Locker Jacomine , Oberwinkler Heike , Eckhardt Manon , Homann Stefanie , Andrew Amy , Strebel Klaus , Kräusslich Hans-Georg 
Published: February 2010

ABSTRACTCD317/Bst-2/tetherin is a host factor that restricts the release of human immunodeficiency virus type 1 (HIV-1) by trapping virions at the plasma membrane of certain producer cells. It is antagonized by the HIV-1 accessory protein Vpu. Previous light microscopy studies localized CD317 to the plasma membrane and the endosomal compartment and showed Vpu induced downregulation. In the present study, we performed quantitative immunoelectron microscopy of CD317 in cells producing wild-type or Vpu-defective HIV-1 and in control cells. Double-labeling experiments revealed that CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network. CD317 largely relocated to endosomes upon HIV-1 infection, and this effect was partly counteracted by Vpu. Unexpectedly, CD317 was enriched in the membrane of viral buds and cell-associated and cell-free viruses compared to the respective plasma membrane, and this enrichment was independent of Vpu. These results suggest that the tethering activity of CD317 critically depends on its density at the cell surface and appears to be less affected by its density in the virion membrane.
Influences of principal stress direction and intermediate principal stress on the stress–strain–strength behaviour of completely decomposed granite
Authors: Kumruzzaman Md. , Yin Jian-Hua 
Published: February 2010

The measurement and study of the stress–strain–strength behaviour of soils in general stress states involving the change of magnitudes and direction of the principal stresses are necessary and important. To investigate the strength behaviour under such conditions, consolidated undrained tests on remoulded hollow cylinder specimens of completely decomposed granite (CDG) were carried out using a hollow cylinder apparatus. Tests were conducted by maintaining a fixed principal stress direction with angle α from the vertical direction together with a fixed value of intermediate principal stress coefficient b. It is observed that the value of the friction angle decreases with an increase in α and the failure surface is anisotropic. There is an increase in friction angle with an increase in b value up to b = 0.25, and the friction angles are almost the same for b > 0.25. In addition, the behaviour of the soil in an undrained simple shear condition was examined. The simple shear condition is very near to the condition of α = 45° and b = 0.25. After having analyzed the test results of all hollow cylinder specimens, it was found that the strength anisotropy is very strong and is dependent on the principal stress direction and intermediate principal stress coefficient.
Description and numerical modelling of the October 2000 Nora debris flow, Northwestern Italian Alps
Authors: Pirulli Marina , Marco Federica 
Published: February 2010

The Nora alluvial fan, which is located in the Orco River valley (Piedmont region, Italy), was affected by a debris flow of approximately 10 000 m3 in October 2000. The event was triggered by heavy rainfall that affected the whole Piedmont region at that time. The mobilization of the water-satured altered gneissic bedrock and colluvium in the upper zone of the Nora basin resulted in the detachment of a debris slide, which rapidly evolved into a channelized noncohesive debris flow. As information from post-event surveys and two pre-event digital elevation models (DEMs), with different resolutions, were available for the study site, the dynamics of the event has been numerically back-analyzed using the numerical code RASH3D. The obtained results have shown both the capability of the code to simulate the dynamics of a noncohesive debris flow, including the final deposit depth distribution, and the importance of on-site surveys and digital elevation model (DEM) resolution in interpreting numerical results and the associated calibrated rheological parameters.
Cinq nouveaux fragments nominaux du traité de Porphyre “Contre les chrétiens”
Authors: Goulet Richard 
Published: February 2010

AbstractFirst publication of five fragments from Porphyry’s treatise Against the Christians discovered in Michael Psellus, Michael Glykas and Damascenus Studites. These objections are explicitly attributed to Porphyry and bear on biblical verses known to have been attacked by this opponent to christianity.
A TAD better for myeloma therapy?
Authors: Giralt Sergio 
Published: February 2010

Abstract
In this issue of Blood, Lokhorst and colleagues report on the results of HOVON-50, a phase 3 randomized trial designed to evaluate the effects of thalidomide during induction treatment and as maintenance in patients with multiple myeloma. There were 556 patients randomly assigned either to 3 cycles of VAD or to TAD. All patients were to receive high-dose melphalan with autologous stem cell support followed by maintenance with interferon for the VAD arm or thalidomide for the TAD arm.1 This study together with other randomized and nonrandomized trials establish a definitive role for thalidomide as induction therapy in conjunction with dexamethasone, anthracyclines, and alkylating agents.
A novel KIR-associated function: evidence that CpG DNA uptake and shuttling to early endosomes is mediated by KIR3DL2
Authors: Sivori Simona , Falco Michela , Carlomagno Simona , Romeo Elisa , Soldani Cristiana , Bensussan Armand , Viola Antonella , Moretta Lorenzo , Moretta Alessandro 
Published: February 2010

AbstractHuman natural killer (NK) cells express Toll-like receptor 9 (TLR9) transcript and, upon exposure to microbial CpG oligodeoxynucleotide (ODN), release cytokines and kill target cells. Here we show that NK cell treatment with CpG ODN results in down-modulation of KIR3DL2 inhibitory receptor from the cell surface and in its cointernalization with CpG ODN. CpG ODN–induced interferon-γ (IFN-γ) release is mostly confined to KIR3DL2+ NK cells, thus suggesting a crucial role of KIR3DL2 in CpG ODN–mediated NK responses. Using soluble receptor molecules, we demonstrate the direct binding of KIR3DL2 to ODNs and we show that the D0 domain is involved primarily in this interaction. KIR3DL2 modulation is also induced in malignant cells of Sézary cutaneous T-cell lymphoma, a disease in which KIR3DL2 represents a typical marker of malignant T cells. Confocal microscopy analysis suggests that, in human NK cells, CpG ODN can encounter TLR9 in early endosomes after being shuttled to these sites by KIR3DL2, which functions as a CpG ODN receptor at the cell surface. This novel KIR-associated function emphasizes the antimicrobial role of NK cells in the course of infection.
The zebrafish genome encodes the largest vertebrate repertoire of functional aquaporins with dual paralogy and substrate specificities similar to mammals
Authors: Tingaud-Sequeira Angèle , Calusinska Magdalena , Finn Roderick N , Chauvigné François , Lozano Juanjo , Cerdà Joan 
Published: February 2010

Abstract

Background
Aquaporins are integral membrane proteins that facilitate the transport of water and small solutes across cell membranes. These proteins are vital for maintaining water homeostasis in living organisms. In mammals, thirteen aquaporins (AQP0-12) have been characterized, but in lower vertebrates, such as fish, the diversity, structure and substrate specificity of these membrane channel proteins are largely unknown.

Results
The screening and isolation of transcripts from the zebrafish (Danio rerio) genome revealed eighteen sequences structurally related to the four subfamilies of tetrapod aquaporins, i.e., aquaporins (AQP0, -1 and -4), water and glycerol transporters or aquaglyceroporins (Glps; AQP3 and AQP7-10), a water and urea transporter (AQP8), and two unorthodox aquaporins (AQP11 and -12). Phylogenetic analyses of nucleotide and deduced amino acid sequences demonstrated dual paralogy between teleost and human aquaporins. Three of the duplicated zebrafish isoforms have unlinked loci, two have linked loci, while DrAqp8 was found in triplicate across two chromosomes. Genomic sequencing, structural analysis, and maximum likelihood reconstruction, further revealed the presence of a putative pseudogene that displays hybrid exons similar to tetrapod AQP5 and -1. Ectopic expression of the cloned transcripts in Xenopus laevis oocytes demonstrated that zebrafish aquaporins and Glps transport water or water, glycerol and urea, respectively, whereas DrAqp11b and -12 were not functional in oocytes. Contrary to humans and some rodents, intrachromosomal duplicates of zebrafish AQP8 were water and urea permeable, while the genomic duplicate only transported water. All aquaporin transcripts were expressed in adult tissues and found to have divergent expression patterns. In some tissues, however, redundant expression of transcripts encoding two duplicated paralogs seems to occur.

Conclusion
The zebrafish genome encodes the largest repertoire of functional vertebrate aquaporins with dual paralogy to human isoforms. Our data reveal an early and specific diversification of these integral membrane proteins at the root of the crown-clade of Teleostei. Despite the increase in gene copy number, zebrafish aquaporins mostly retain the substrate specificity characteristic of the tetrapod counterparts. Based upon the integration of phylogenetic, genomic and functional data we propose a new classification for the piscine aquaporin superfamily.
Positive selection neighboring functionally essential sites and disease-implicated regions of mammalian reproductive proteins
Authors: Morgan Claire C , Loughran Noeleen B , Walsh Thomas A , Harrison Alan J , O'Connell Mary J 
Published: February 2010

AbstractBackgroundReproductive proteins are central to the continuation of all mammalian species. The evolution of these proteins has been greatly influenced by environmental pressures induced by pathogens, rival sperm, sexual selection and sexual conflict. Positive selection has been demonstrated in many of these proteins with particular focus on primate lineages. However, themammaliaare a diverse group in terms of mating habits, population sizes and germ line generation times. We have examined the selective pressures at work on a number of novel reproductive proteins across a wide variety ofmammalia.ResultsWe show that selective pressures on reproductive proteins are highly varied. Of the 10 genes analyzed in detail, all contain signatures of positive selection either across specific sites or in specific lineages or a combination of both. Our analysis of SP56 and Col1a1 are entirely novel and the results show positively selected sites present in each gene. Our findings for the Col1a1 gene are suggestive of a link between positive selection and severe disease type. We find evidence in our dataset to suggest that interacting proteins are evolving in symphony: most likely to maintain interacting functionality.ConclusionOurin silicoanalyses show positively selected sites are occurring near catalytically important regions suggesting selective pressure to maximize efficient fertilization. In those cases where a mechanism of protein function is not fully understood, the sites presented here represent ideal candidates for mutational study. This work has highlighted the widespread rate heterogeneity in mutational rates across themammaliaand specifically has shown that the evolution of reproductive proteins is highly varied depending on the species and interacting partners. We have shown that positive selection and disease are closely linked in the Col1a1 gene.
Dopamine D2 receptor polymorphisms and susceptibility to alcohol dependence in Indian males: a preliminary study
Authors: Prasad Pushplata , Ambekar Atul , Vaswani Meera 
Published: February 2010

Abstract

Background
Dopamine is an important neurotransmitter involved in reward mechanism in the brain and thereby influences development and relapse of alcohol dependence. The dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been found to be associated with increased alcohol consumption through mechanisms involving incentive salience attributions and craving in alcoholic patients. Therefore, we investigated the association of three single nucleotide polymorphisms (SNP) in DRD2 gene with alcohol dependence in the north Indian subjects.

Methods
In a retrospective analysis, genetic association of three polymorphisms from DRD2 gene with alcohol dependence was investigated using a case-control approach. Alcohol dependence was determined by DSM-IV criteria and a total of 90 alcoholics and 60 healthy unrelated age-matched control subjects were recruited. Odds ratio and confidence interval was calculated to determine risk conferred by a predisposing allele/genotype/haplotype. Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair-wise interactions between SNPs.

Results
The study showed a significant association of -141C Ins allele and a trend of association of TaqI A1 allele of DRD2 with alcohol dependence. Haplotype with the predisposing -141C Ins and TaqI A1 alleles (-141C Ins-A-A1) seems to confer ≈ 2.5 times more risk to develop alcohol dependence.

Conclusions
The study provides preliminary insight into genetic risk to alcohol dependence in Indian males. Two polymorphisms namely, -141C Ins/Del and TaqI A in DRD2 gene may have clinical implications among Indian alcoholic subjects.
Mitotic slippage in non-cancer cells induced by a microtubule disruptor, disorazole C1
Authors: Xu Fengfeng L , Rbaibi Youssef , Kiselyov Kirill , Lazo John S , Wipf Peter , Saunders William S 
Published: February 2010

Abstract

Background
Disorazoles are polyene macrodiolides isolated from a myxobacterium fermentation broth. Disorazole C1 was newly synthesized and found to depolymerize microtubules and cause mitotic arrest. Here we examined the cellular responses to disorazole C1 in both non-cancer and cancer cells and compared our results to vinblastine and taxol.

Results
In non-cancer cells, disorazole C1 induced a prolonged mitotic arrest, followed by mitotic slippage, as confirmed by live cell imaging and cell cycle analysis. This mitotic slippage was associated with cyclin B degradation, but did not require p53. Four assays for apoptosis, including western blotting for poly(ADP-ribose) polymerase cleavage, microscopic analyses for cytochrome C release and annexin V staining, and gel electrophoresis examination for DNA laddering, were conducted and demonstrated little induction of apoptosis in non-cancer cells treated with disorazole C1. On the contrary, we observed an activated apoptotic pathway in cancer cells, suggesting that normal and malignant cells respond differently to disorazole C1.

Conclusion
Our studies demonstrate that non-cancer cells undergo mitotic slippage in a cyclin B-dependent and p53-independent manner after prolonged mitotic arrest caused by disorazole C1. In contrast, cancer cells induce the apoptotic pathway after disorazole C1 treatment, indicating a possibly significant therapeutic window for this compound.