bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of the Inaccurate Assignment of Mixed Infections by Mycobacterium tuberculosis as Exogenous Reinfection and Analysis of the Potential Role of Bacterial Factors in Reinfection
Authors: Martín Ana , Herranz Marta , Navarro Yurena , Lasarte Sandra , Ruiz Serrano María Jesús , Bouza Emilio , García de Viedma Darío 
Published: February 2011

ABSTRACTMolecular analysis of recurrent tuberculosis has revealed that a second episode may be caused by a strain ofMycobacterium tuberculosisother than that involved in the first infection, thus indicating that exogenous reinfection plays a role in recurrence. We focused on two aspects of reinfection that have received little attention. First, we evaluated whether a lack of methodological refinement could lead to inaccurate assignment of mixed infections as exogenous reinfection, in which a differential selection of each of the coinfecting strains occurred over time. We used the mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) method to genotype 122 isolates from 40 patients with recurrent tuberculosis. We identified 11/40 (27.5%) cases with genotypic differences between the isolates involved in the sequential episodes. Major genotypic differences were found in 8/11 cases, suggesting exogenous reinfection; in the remaining 3 cases, subtle genotypic differences were observed, probably indicating microevolution from a parental strain. In all cases, only a single strain was detected for the isolate(s) from each episode, thus ruling out the possibility that reinfection could correspond to undetected mixed infection. Second, we analyzed the infectivity of a selection of 12 strains from six cases with genotypically different strains between episodes. No main differences were observed in anex vivomodel of infection between the strains involved in the first episodes and those involved in the recurrent episodes. In our setting, our results suggest the following: (i) the possibility of misassignment of mixed infection as exogenous reinfection is improbable, and (ii) bacterial infectivity does not seem to play a role in exogenous reinfection.
pO157_Sal, a Novel Conjugative Plasmid Detected in Outbreak Isolates of Escherichia coli O157:H7
Authors: Wang Ping , Xiong Yanwen , Lan Ruiting , Ye Changyun , Wang Hua , Ren Jun , Jing Huaiqi , Wang Yiting , Zhou Zhemin , Cui Zhigang , Zhao Hongqing , Chen Yuli , Jin Dong , Bai Xuemei , Zhao Ailan , Wang Yan , Zhang Shaomin , Sun Hui , Li Juan , Wang Tao , Wang Lei , Xu Jianguo 
Published: February 2011

ABSTRACT

In addition to the large virulence plasmid pO157, a novel 38-kb conjugative plasmid, pO157_Sal, was identified and sequenced from an
Escherichia coli
O157:H7 outbreak-associated Chinese isolate that shares high similarity with a plasmid in
Salmonella enterica
serovar Agona. The plasmid was found in 15 of 326 isolates, 12 of which were of the same pulsed-field gel electrophoresis type.
Mobility and Interactions of Coronavirus Nonstructural Protein 4
Authors: Hagemeijer Marne C. , Ulasli Mustafa , Vonk Annelotte M. , Reggiori Fulvio , Rottier Peter J. M. , de Haan Cornelis A. M. 
Published: February 2011

ABSTRACT
Green fluorescent protein (GFP)-tagged mouse hepatitis coronavirus nonstructural protein 4 (nsp4) was shown to localize to the endoplasmic reticulum (ER) and to be recruited to the coronavirus replicative structures. Fluorescence loss in photobleaching and fluorescence recovery after photobleaching experiments demonstrated that while the membranes of the ER are continuous with those harboring the replicative structures, the mobility of nsp4 at the latter structures is relatively restricted. In agreement with that observation, nsp4 was shown to be engaged in homotypic and heterotypic interactions, the latter with nsp3 and nsp6. In addition, the coexpression of nsp4 with nsp3 affected the subcellular localization of the two proteins.
Design of Chimeric Alphaviruses with a Programmed, Attenuated, Cell Type-Restricted Phenotype
Authors: Kim Dal Young , Atasheva Svetlana , Foy Niall J. , Wang Eryu , Frolova Elena I. , Weaver Scott , Frolov Ilya 
Published: February 2011

ABSTRACT

The
Alphavirus
genus in the
Togaviridae
family contains a number of human and animal pathogens. The importance of alphaviruses has been strongly underappreciated; however, epidemics of chikungunya virus (CHIKV), causing millions of cases of severe and often persistent arthritis in the Indian subcontinent, have raised their profile in recent years. In spite of a continuous public health threat, to date no licensed vaccines have been developed for alphavirus infections. In this study, we have applied an accumulated knowledge about the mechanism of alphavirus replication and protein function in virus-host interactions to introduce a new approach in designing attenuated alphaviruses. These variants were constructed from genes derived from different, geographically isolated viruses. The resulting viable variants encoded CHIKV envelope and, in contrast to naturally circulating viruses, lacked the important contributors to viral pathogenesis: genes encoding proteins functioning in inhibition of cellular transcription and downregulation of the cellular antiviral response. To make these viruses incapable of transmission by mosquito vectors and to differentially regulate expression of viral structural proteins, their replication was made dependent on the internal ribosome entry sites, derived from other positive-polarity RNA (RNA
+
) viruses. The rational design of the genomes was complemented by selection procedures, which adapted viruses to replication in tissue culture and produced variants which (i) demonstrated different levels of replication and production of the individual structural proteins, (ii) efficiently induced the antiviral response in infected cells, (iii) were incapable of replication in cells of mosquito origin, and (iv) efficiently replicated in Vero cells. This modular approach to genome design is applicable for the construction of other alphaviruses with a programmed, irreversibly attenuated phenotype.
HIV-1 Escape from the CCR5 Antagonist Maraviroc Associated with an Altered and Less-Efficient Mechanism of gp120-CCR5 Engagement That Attenuates Macrophage Tropism
Authors: Roche Michael , Jakobsen Martin R. , Sterjovski Jasminka , Ellett Anne , Posta Filippo , Lee Benhur , Jubb Becky , Westby Mike , Lewin Sharon R. , Ramsland Paul A. , Churchill Melissa J. , Gorry Paul R. 
Published: February 2011

ABSTRACT

Maraviroc (MVC) inhibits the entry of human immunodeficiency virus type 1 (HIV-1) by binding to and modifying the conformation of the CCR5 extracellular loops (ECLs). Resistance to MVC results from alterations in the HIV-1 gp120 envelope glycoproteins (Env) enabling recognition of the drug-bound conformation of CCR5. To better understand the mechanisms underlying MVC resistance, we characterized the virus-cell interactions of gp120 from
in vitro
-generated MVC-resistant HIV-1 (MVC-Res Env), comparing them with those of gp120 from the sensitive parental virus (MVC-Sens Env). In the absence of the drug, MVC-Res Env maintains a highly efficient interaction with CCR5, similar to that of MVC-Sens Env, and displays a relatively modest increase in dependence on the CCR5 N terminus. However, in the presence of the drug, MVC-Res Env interacts much less efficiently with CCR5 and becomes critically dependent on the CCR5 N terminus and on positively charged elements of the drug-modified CCR5 ECL1 and ECL2 regions (His88 and His181, respectively). Structural analysis suggests that the Val323 resistance mutation in the gp120 V3 loop alters the secondary structure of the V3 loop and the buried surface area of the V3 loop–CCR5 N terminus interface. This altered mechanism of gp120-CCR5 engagement dramatically attenuates the entry of HIV-1 into monocyte-derived macrophages (MDM), cell-cell fusion activity in MDM, and viral replication capacity in MDM. In addition to confirming that HIV-1 escapes MVC by becoming heavily dependent on the CCR5 N terminus, our results reveal novel interactions with the drug-modified ECLs that are critical for the utilization of CCR5 by MVC-Res Env and provide additional insights into virus-cell interactions that modulate macrophage tropism.
Cytomegalovirus UL103 Controls Virion and Dense Body Egress
Authors: Ahlqvist Jenny , Mocarski Edward 
Published: February 2011

ABSTRACT

Human cytomegalovirus UL103 encodes a tegument protein that is conserved across herpesvirus subgroups. Mutant viruses lacking this gene product exhibit dramatically reduced accumulation of cell-free virus progeny and poor cell-to-cell spread. Given that viral proteins and viral DNA accumulate with normal kinetics in cells infected with mutant virus, UL103 appears to function during the late phase of replication, playing a critical role in egress of capsidless dense bodies and virions. Few dense bodies were observed in the extracellular space in mutant virus-infected cells in the presence or absence of the DNA encapsidation inhibitor 2-bromo-5,6-dichloro-1-(β-
d
-ribofuranosyl)benzimidazole. Upon reversal of encapsidation inhibition, UL103 had a striking impact on accumulation of cell-free virus, but not on accumulation of cell-associated virus. Thus, UL103 plays a novel and important role during maturation, regulating virus particle and dense body egress from infected cells.
A 128-Base-Pair Sequence Containing the
pac1
and a Presumed Cryptic
pac2
Sequence Includes
cis
Elements Sufficient To Mediate Efficient Genome Maturation of Human Cytomegalovirus
Authors: Wang Jian Ben , McVoy Michael A. 
Published: February 2011

ABSTRACT

Herpesvirus DNA replication proceeds via concatemeric replicative intermediates that are comprised of head-to-tail linked genomes. Genome maturation is carried out by the terminase, an enzyme complex that mediates both the insertion of concatemer DNA into capsids and its subsequent cleavage to release genomes within these capsids. This cleavage is sequence specific, but the governing
cis
-acting DNA sequences are only partially characterized. Two highly conserved motifs, the
pac1
and
pac2
motifs, lie near the ends of herpesvirus genomes and are known to be critical for genome maturation. In murine cytomegalovirus, poorly conserved sequences distal to the
pac2
motif up to 150 bp from the point of cleavage are also important for cleavage. Here, we sought to identify the cleavage/packaging signals of human cytomegalovirus. Our results show that a previously proposed
pac2
-like poly(A) tract is dispensable for cleavage/packaging function and suggest that human cytomegalovirus may utilize a cryptic
pac2
motif that lacks a poly(A) tract characteristic of
pac2
motifs in other herpesviruses. Additional distal sequences 47 to 100 bp from the point of cleavage were found to enhance cleavage efficiency. These results should facilitate the identification of
trans
-acting factors that bind to these
cis
elements and elucidation of their functions. Such information will be critical for understanding the molecular basis of this complex process.
Adenovirus Core Protein VII Protects the Viral Genome from a DNA Damage Response at Early Times after Infection
Authors: Karen Kasey A. , Hearing Patrick 
Published: February 2011

ABSTRACT
Adenovirus has a linear, double-stranded DNA genome that is perceived by the cellular Mre11-Rad50-Nbs1 (MRN) DNA repair complex as a double-strand break. If unabated, MRN elicits a double-strand break repair response that blocks viral DNA replication and ligates the viral genomes into concatemers. There are two sets of early viral proteins that inhibit the MRN complex. The E1B-55K/E4-ORF6 complex recruits an E3 ubiquitin ligase and targets MRN proteins for proteasome-dependent degradation. The E4-ORF3 protein inhibits MRN through sequestration. The mechanism that prevents MRN recognition of the viral genome prior to the expression of these early proteins was previously unknown. Here we show a temporal correlation between the loss of viral core protein VII from the adenovirus genome and a gain of checkpoint signaling due to the double-strand break repair response. While checkpoint signaling corresponds to the recognition of the viral genome, core protein VII binding to and checkpoint signaling at viral genomes are largely mutually exclusive. Transcription is known to release protein VII from the genome, and the inhibition of transcription shows a decrease in checkpoint signaling. Finally, we show that the nuclease activity of Mre11 is dispensable for the inhibition of viral DNA replication during a DNA damage response. These results support a model involving the protection of the incoming viral genome from checkpoint signaling by core protein VII and suggest that the induction of an MRN-dependent DNA damage response may inhibit adenovirus replication by physically masking the origins of DNA replication rather than altering their integrity.
Insights into Polyomaviridae MicroRNA Function Derived from Study of the Bandicoot Papillomatosis Carcinomatosis Viruses
Authors: Chen Chun Jung , Kincaid Rodney P. , Seo Gil Ju , Bennett Mark D. , Sullivan Christopher S. 
Published: February 2011

ABSTRACT

Several different members of the
Polyomaviridae
, including some human pathogens, encode microRNAs (miRNAs) that lie antisense with respect to the early gene products, the tumor (T) antigens. These miRNAs negatively regulate T antigen expression by directing small interfering RNA (siRNA)-like cleavage of the early transcripts. miRNA mutant viruses of some members of the
Polyomaviridae
express increased levels of early proteins during lytic infection. However, the importance of miRNA-mediated negative regulation of the T antigens remains uncertain. Bandicoot papillomatosis carcinomatosis virus type 1 (BPCV1) is associated with papillomas and carcinomas in the endangered marsupial the western barred bandicoot (
Perameles bougainville
). BPCV1 is the founding member of a new group of viruses that remarkably share distinct properties in common with both the polyomavirus and papillomavirus families. Here, we show that BPCV1 encodes, in the same orientation as the papillomavirus-like transcripts, a miRNA located within a long noncoding region (NCR) of the genome. Furthermore, this NCR serves the function of both promoter and template for the primary transcript that gives rise to the miRNA. Unlike the polyomavirus miRNAs, the BPCV1 miRNA is not encoded antisense to the T antigen transcripts but rather lies in a separate, proximal region of the genome. We have mapped the 3′ untranslated region (UTR) of the BPCV1 large T antigen early transcript and identified a functional miRNA target site that is imperfectly complementary to the BPCV1 miRNA. Chimeric reporters containing the entire BPCV1 T antigen 3′ UTR undergo negative regulation when coexpressed with the BPCV1 miRNA. Notably, the degree of negative regulation observed is equivalent to that of an identical reporter that is engineered to bind to the BPCV1 miRNA with perfect complementarity. We also show that this miRNA and this novel mode of early gene regulation are conserved with the related BPCV2. Finally, papillomatous lesions from a western barred bandicoot express readily detectable levels of this miRNA, stressing its likely importance
in vivo
. Combined, the alternative mechanisms of negative regulation of T antigen expression between the BPCVs and the polyomaviruses support the importance of miRNA-mediated autoregulation in the life cycles of some divergent polyomaviruses and polyomavirus-like viruses.
Role of CCL-2, CCR-2 and CCR-4 in cerulein-induced acute pancreatitis and pancreatitis-associated lung injury
Authors: Frossard Jean Louis , Lenglet Sébastien , Montecucco Fabrizio , Steffens Sabine , Galan Katia , Pelli Graziano , Spahr Laurent , Mach Francois , Hadengue Antoine 
Published: February 2011

Background and aimsAcute pancreatitis is an inflammatory process of variable severity. Leucocytes are thought to play a key role in the development of pancreatitis and pancreatitis-associated lung injury. The interactions between inflammatory cells and their mediators are crucial for determining tissue damage. Monocyte chemoattractant protein-1 (or CCL-2), CCR-2 and CCR-4 are chemokines and chemokine receptors involved in leucocyte trafficking. The aim of the study was to evaluate the role of the CCL-2, CCR-2 and CCR-4 chemokine receptors in the pathogenesis of cerulein-induced pancreatitis and pancreatitis-associated lung injury. To address the role of CCL-2, CCR-2 and CCR-4 that attracts leucocytes cells in inflamed tissues, pancreatitis was induced by administering supramaximal doses of cerulein in mice that do not express CCL-2, CCR-2 or CCR-4.MethodsThe severity of pancreatitis was measured by serum amylase, pancreatic oedema and acinar cell necrosis. Lung injury was quantitated by evaluating lung microvascular permeability and lung myeloperoxidase activity. Chemokine and chemokine-receptor expression were quantitated by real-time PCR. The nature of inflammatory cells invading the pancreas and lungs was studied by immunostaining.ResultsThe authors have found that pancreas CCL-2 and CCR-2 levels rise during pancreatitis. Both pancreatitis and the associated lung injury are blunted, but not completely prevented, in mice deficient in CCL-2, whereas the deficiency in either CCR-2 or CCR-4 does not reduce the severity of both the pancreatitis and the lung injury. The amounts of neutrophils and monocyte/macrophages (MOMA)-2 cells were significantly lower in mice deficient in CCL-2 compared with their sufficient littermates.ConclusionsThese results suggest that CCL-2 plays a key role in pancreatitis by modulating the infiltration by neutrophils and MOMA-2 cells, and that its deficiency may improve the outcome of the disease.
Neoproterozoic loess and limits to snowball Earth
Authors: Retallack Gregory J. 
Published: February 2011

Abstract:
Neoproterozoic tillites overlain by limestones and dolostones (cap carbonates) have been interpreted as evidence of abrupt climate change from glaciers to tropical seas on the assumption that cap carbonates were marine. This assumption is here challenged by evidence for loess deposition of the Nuccaleena Formation of South Australia from granulometry (angular, randomly oriented, silt, modal diameter 7ϕ) and sedimentary structures (climbing-translatent cross-stratification, linear dunes). In addition, a variety of palaeosols in the Nuccaleena Formation have red clayey horizons, replacive micritization, expansion cracks, and thufur mounds, as well as low carbon and oxygen isotope values, high strontium isotope ratios, and geochemical evidence of leaching and clay formation. This cap carbonate has no definitively marine features, and is here interpreted as periglacial loess overlying the fluvioglacial–intertidal Elatina Formation, so it is not a record of abrupt global warming from snowball Earth. Other cap carbonates around the world differ in various ways, and may have formed in different depositional environments, but could profitably be reconsidered from the new perspective of the loess depositional model proposed here.

Supplementary material:

Tabular comparison of marine and non-marine interpretations of cap carbonates, petrographic textures and composition, and new isotopic and chemical analyses of Nuccaleena Formation are available at
http:/www.geolsoc.org.uk/SUP18443
.
A Gene Expression Signature from Human Breast Cancer Cells with Acquired Hormone Independence Identifies MYC as a Mediator of Antiestrogen Resistance
Authors: Miller Todd W. , Balko Justin M. , Ghazoui Zara , Dunbier Anita , Anderson Helen , Dowsett Mitch , González-Angulo Ana M. , Mills Gordon B. , Miller William R. , Wu Huiyun , Shyr Yu , Arteaga Carlos L. 
Published: February 2011

AbstractPurpose: Although most patients with estrogen receptor α (ER)-positive breast cancer initially respond to endocrine therapy, many ultimately develop resistance to antiestrogens. However, mechanisms of antiestrogen resistance and biomarkers predictive of such resistance are underdeveloped.Experimental Design: We adapted four ER+ human breast cancer cell lines to grow in an estrogen-depleted medium. A gene signature of estrogen independence was developed by comparing expression profiles of long-term estrogen-deprived (LTED) cells to their parental counterparts. We evaluated the ability of the LTED signature to predict tumor response to neoadjuvant therapy with an aromatase inhibitor and disease outcome following adjuvant tamoxifen. We utilized Gene Set Analysis (GSA) of LTED cell gene expression profiles and a loss-of-function approach to identify pathways causally associated with resistance to endocrine therapy.Results: The LTED gene expression signature was predictive of high tumor cell proliferation following neoadjuvant therapy with anastrozole and letrozole, each in different patient cohorts. This signature was also predictive of poor recurrence-free survival in two studies of patients treated with adjuvant tamoxifen. Bioinformatic interrogation of expression profiles in LTED cells revealed a signature of MYC activation. The MYC activation signature and high MYC protein levels were both predictive of poor outcome following tamoxifen therapy. Finally, knockdown of MYC inhibited LTED cell growth.Conclusions: A gene expression signature derived from ER+ breast cancer cells with acquired hormone independence predicted tumor response to aromatase inhibitors and associated with clinical markers of resistance to tamoxifen. Activation of the MYC pathway was associated with this resistance. Clin Cancer Res; 17(7); 2024–34. ©2011 AACR.
The empirical study of a four-row heat pipe heat exchanger to predict the year-round energy recovery in the tropics
Authors: Yau YH , Ahmadzadehtalatapeh M 
Published: February 2011

The effect of heat pipe heat exchanger on the heat recovery was studied in the tropics. The performance of the heat exchanger was monitored during the one week of operation (168 h) to find out the performance characteristic curves. Three coil face velocities namely, 2, 2.2 and 2.5 m/s were tested and the temperature of return air was controlled at 24°C. The relevant empirical equations were then employed for the hour-by-hour prediction of the energy recovery by the heat pipe heat exchanger for the whole year. The impact of inside design temperature on the heat recovery by the heat exchanger was also studied. The thermal performance of the heat pipe heat exchanger was simulated based on the effectiveness-NTU method and the theoretical values were compared with the experimental data. Practical application: Performance improvement of the heating, ventilating and air conditioning systems is a challenge to the designers. The results obtained from this research work could serve as a practical guide for engineers who are intending to use heat pipe heat exchangers in the heating, ventilation and air conditioning systems operating in tropical climates. Engineers and researchers have the potential to use the recommended empirical performance equations to examine the impact of heat pipe heat exchangers on the performance of the current air conditioning systems. Moreover, these empirical performance equations enable the year-round operating effect of heat pipe heat exchangers on energy savings to be predicted realistically.