bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Herpes Simplex Virus 1 vhs Protein Enhances Translation of Viral True Late mRNAs and Virus Production in a Cell Type-Dependent Manner
Authors: Dauber Bianca , Pelletier Jerry , Smiley James R. 
Published: March 2011

ABSTRACT
The herpes simplex virus 1 (HSV-1) virion host shutoff protein (vhs) degrades viral and cellular mRNAs. Here, we demonstrate for the first time that vhs also boosts translation of viral true late mRNAs in a cell type-dependent manner and that this effect determines the viral growth phenotype in the respective cell type. Our study was prompted by the detection of stress granules, indicators of stalled translation initiation, in cells infected with vhs mutants but not in wild-type-virus-infected cells. Accumulation of true late-gene products gC and US11 was strongly reduced in the absence of vhs in HeLa cells and several other restrictive cell lines but not in Vero and other permissive cells and was independent of phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Polysome analysis showed that gC and US11 transcripts were poorly translated in vhs-null-virus-infected HeLa cells, while translation of a cellular mRNA was not affected. Interestingly, hippuristanol, an eIF4A inhibitor, produced a similar phenotype in HeLa cells infected with wild-type HSV-1, while Vero cells were much more resistant to the inhibitor. These results suggest that translation of true late-gene transcripts is particularly sensitive to conditions of limited access to translation factors and that vhs is able either to prevent the limiting conditions or to facilitate translation initiation under these conditions. The varied permissivity of cell lines to vhs-null infection may stem from differences in the resilience of the translation machinery or the ability to control the accumulation of mRNAs.
Activation of the Alphavirus Spike Protein Is Suppressed by Bound E3
Authors: Sjöberg Mathilda , Lindqvist Birgitta , Garoff Henrik 
Published: March 2011

ABSTRACT

Alphaviruses are taken up into the endosome of the cell, where acidic conditions activate the spikes for membrane fusion. This involves dissociation of the three E2-E1 heterodimers of the spike and E1 interaction with the target membrane as a homotrimer. The biosynthesis of the heterodimer as a pH-resistant p62-E1 precursor appeared to solve the problem of premature activation in the late and acidic parts of the biosynthetic transport pathway in the cell. However, p62 cleavage into E2 and E3 by furin occurs before the spike has left the acidic compartments, accentuating the problem. In this work, we used a furin-resistant Semliki Forest virus (SFV) mutant, SFV
SQL
, to study the role of E3 in spike activation. The cleavage was reconstituted with proteinase K
in vitro
using free virus or spikes on SFV
SQL
-infected cells. We found that E3 association with the spikes was pH dependent, requiring acidic conditions, and that the bound E3 suppressed spike activation. This was shown in an
in vitro
spike activation assay monitoring E1 trimer formation with liposomes and a fusion-from-within assay with infected cells. Furthermore, the wild type, SFV
wt
, was found to bind significant amounts of E3, especially if produced in dense cultures, which lowered the pH of the culture medium. This E3 also suppressed spike activation. The results suggest that furin-cleaved E3 continues to protect the spike from premature activation in acidic compartments of the cell and that its release in the neutral extracellular space primes the spike for low-pH activation.
Identification of a Single Amino Acid Required for APOBEC3 Antiretroviral Cytidine Deaminase Activity
Authors: Dang Ying , Abudu Aierken , Son SungMo , Harjes Elena , Spearman Paul , Matsuo Hiroshi , Zheng Yong-Hui 
Published: March 2011

ABSTRACT
During studies of APOBEC3 (A3) anti-human immunodeficiency virus type 1 (anti-HIV-1) mechanisms, we identified a single cysteine at position 320 (C320) that disrupts A3DE activity. This residue is located in the recently identified DNA binding domain in A3G. Replacing C320 with a corresponding tyrosine from A3F (Y307) increased A3DE antiviral activity more than 20-fold. Conversely, replacing A3F Y307 with a cysteine or inserting a similar cysteine into A3B or A3G disrupted the anti-HIV activity of A3. Further investigation uncovered that C320 significantly reduces A3DE catalytic activity.
Caveolin 1 Inhibits HIV Replication by Transcriptional Repression Mediated through NF-κB
Authors: Wang Xiao Mei , Nadeau Peter E. , Lin Shanshan , Abbott Jeffrey R. , Mergia Ayalew 
Published: March 2011

ABSTRACTCaveolin 1 (Cav-1), the scaffold protein of a specific membrane lipid raft called caveolae, has been reported to suppress HIV-1 replication. However, the mechanism by which Cav-1 inhibits HIV replication remains unclear. In this study, we investigated the mechanism by which Cav-1 inhibits HIV replication at the level of gene expression. Our results show that Cav-1 represses viral gene expression and that this suppression involves the NF-κB pathway. We used several approaches in different cell types, including primary CD4+T cells and macrophages, to demonstrate the role of nuclear factor κB (NF-κB) in Cav-1-mediated inhibition of viral expression. A mutational analysis of thecis-acting element shows that the two NF-κB sites in the U3 region of the long terminal repeat (LTR) are critical for Cav-1-mediated inhibition of viral expression. In the presence of Cav-1, phosphorylation of IKKβ, IKKα, IκBα, and NF-κB p65 is dramatically reduced, while viral gene expression is suppressed. In addition, translocation of NF-κB p65 to the nucleus decreases substantially in the presence of Cav-1. Furthermore, significant inhibition of NF-κB activation and binding to target DNA are evident in the presence of Cav-1. These results establish evidence that Cav-1 inhibits HIV replication by transcriptional repression of viral gene expression and contributes to HIV's persistent infection of macrophages.
Development and RNA-Synthesizing Activity of Coronavirus Replication Structures in the Absence of Protein Synthesis
Authors: van den Worm Sjoerd H. E. , Knoops Kèvin , Zevenhoven-Dobbe Jessika C. , Beugeling Corrine , van der Meer Yvonne , Mommaas A. Mieke , Snijder Eric J. 
Published: March 2011

ABSTRACT
The RNA replication and transcription complex of coronaviruses is associated with an elaborate reticulovesicular network (RVN) of modified endoplasmic reticulum. Using cycloheximide and puromycin, we have studied the effect of translation inhibition on the RNA synthesis of severe acute respiratory syndrome coronavirus and mouse hepatitis virus. Both inhibitors prevented the usual exponential increase in viral RNA synthesis, with immunofluorescence and electron microscopy indicating that RVN development came to a standstill. Nevertheless, limited RNA synthesis was supported, implying that continued translation is not an absolute requirement and suggesting a direct link between RVN formation and accumulation of coronavirus proteins.
Identification and Characterization of a Ross River Virus Variant That Grows Persistently in Macrophages, Shows Altered Disease Kinetics in a Mouse Model, and Exhibits Resistance to Type I Interferon
Authors: Lidbury Brett A. , Rulli Nestor E. , Musso Cristina M. , Cossetto Susan B. , Zaid Ali , Suhrbier Andreas , Rothenfluh Harald S. , Rolph Michael S. , Mahalingam Suresh 
Published: March 2011

ABSTRACTAlphaviruses, such as chikungunya virus, o'nyong-nyong virus, and Ross River virus (RRV), cause outbreaks of human rheumatic disease worldwide. RRV is a positive-sense single-stranded RNA virus endemic to Australia and Papua New Guinea. In this study, we sought to establish anin vitromodel of RRV evolution in response to cellular antiviral defense mechanisms. RRV was able to establish persistent infection in activated macrophages, and a small-plaque variant (RRVPERS) was isolated after several weeks of culture. Nucleotide sequence analysis of RRVPERSfound several nucleotide differences in the nonstructural protein (nsP) region of the RRVPERSgenome. A point mutation was also detected in the E2 gene. Compared to the parent virus (RRV-T48), RRVPERSshowed significantly enhanced resistance to beta interferon (IFN-β)-stimulated antiviral activity. RRVPERSinfection of RAW 264.7 macrophages induced lower levels of IFN-β expression and production than infection with RRV-T48. RRVPERSwas also able to inhibit type I IFN signaling. Mice infected with RRVPERSexhibited significantly enhanced disease severity and mortality compared to mice infected with RRV-T48. These results provide strong evidence that the cellular antiviral response can direct selective pressure for viral sequence evolution that impacts on virus fitness and sensitivity to alpha/beta IFN (IFN-α/β).
Influence of Host Gene Transcription Level and Orientation on HIV-1 Latency in a Primary-Cell Model
Authors: Shan Liang , Yang Hung-Chih , Rabi S. Alireza , Bravo Hector C. , Shroff Neeta S. , Irizarry Rafael A. , Zhang Hao , Margolick Joseph B. , Siliciano Janet D. , Siliciano Robert F. 
Published: March 2011

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) establishes a latent reservoir in resting memory CD4
+
T cells. This latent reservoir is a major barrier to the eradication of HIV-1 in infected individuals and is not affected by highly active antiretroviral therapy (HAART). Reactivation of latent HIV-1 is a possible strategy for elimination of this reservoir. The mechanisms with which latency is maintained are unclear. In the analysis of the regulation of HIV-1 gene expression, it is important to consider the nature of HIV-1 integration sites. In this study, we analyzed the integration and transcription of latent HIV-1 in a primary CD4
+
T cell model of latency. The majority of integration sites in latently infected cells were in introns of transcription units. Serial analysis of gene expression (SAGE) demonstrated that more than 90% of those host genes harboring a latent integrated provirus were transcriptionally active, mostly at high levels. For latently infected cells, we observed a modest preference for integration in the same transcriptional orientation as the host gene (63.8% versus 36.2%). In contrast, this orientation preference was not observed in acutely infected or persistently infected cells. These results suggest that transcriptional interference may be one of the important factors in the establishment and maintenance of HIV-1 latency. Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4
+
T cells.
Genome-Scale Evolution and Phylodynamics of Equine H3N8 Influenza A Virus
Authors: Murcia Pablo R. , Wood James L. N. , Holmes Edward C. 
Published: March 2011

ABSTRACT
Equine influenza viruses (EIVs) of the H3N8 and H7N7 subtypes are the causative agents of an important disease of horses. While EIV H7N7 apparently is extinct, H3N8 viruses have circulated for more than 50 years. Like human influenza viruses, EIV H3N8 caused a transcontinental pandemic followed by further outbreaks and epidemics, even in populations with high vaccination coverage. Recently, EIV H3N8 jumped the species barrier to infect dogs. Despite its importance as an agent of infectious disease, the mechanisms that underpin the evolutionary and epidemiological dynamics of EIV are poorly understood, particularly at a genomic scale. To determine the evolutionary history and phylodynamics of EIV H3N8, we conducted an extensive analysis of 82 complete viral genomes sampled during a 45-year span. We show that both intra- and intersubtype reassortment have played a major role in the evolution of EIV, and we suggest that intrasubtype reassortment resulted in enhanced virulence while heterosubtypic reassortment contributed to the extinction of EIV H7N7. We also show that EIV evolves at a slower rate than other influenza viruses, even though it seems to be subject to similar immune selection pressures. However, a relatively high rate of amino acid replacement is observed in the polymerase acidic (PA) segment, with some evidence for adaptive evolution. Most notably, an analysis of viral population dynamics provided evidence for a major population bottleneck of EIV H3N8 during the 1980s, which we suggest resulted from changes in herd immunity due to an increase in vaccination coverage.
Persistence of Multiple Genetic Lineages within Intrahost Populations of Ross River Virus
Authors: Liu Wen J. , Rourke Michelle F. , Holmes Edward C. , Aaskov John G. 
Published: March 2011

ABSTRACT
We examined the structure and extent of genetic diversity in intrahost populations of Ross River virus (RRV) in samples from six human patients, focusing on the nonstructural (nsP3) and structural (E2) protein genes. Strikingly, although the samples were collected from contrasting ecological settings 3,000 kilometers apart in Australia, we observed multiple viral lineages in four of the six individuals, which is indicative of widespread mixed infections. In addition, a comparison with previously published RRV sequences revealed that these distinct lineages have been in circulation for at least 5 years, and we were able to document their long-term persistence over extensive geographical distances.
Disclosure of terminal illness to patients and families: diversity of governing codes in 14 Islamic countries
Authors: Abdulhameed Hunida E , Hammami Muhammad M , Hameed Mohamed Elbushra A 
Published: March 2011

BackgroundThe consistency of codes governing disclosure of terminal illness to patients and families in Islamic countries has not been studied until now.ObjectivesTo review available codes on disclosure of terminal illness in Islamic countries.Data source and extractionData were extracted through searches on Google and PubMed. Codes related to disclosure of terminal illness to patients or families were abstracted, and then classified independently by the three authors.Data synthesisCodes for 14 Islamic countries were located. Five codes were silent regarding informing the patient, seven allowed concealment, one mandated disclosure and one prohibited disclosure. Five codes were silent regarding informing the family, four allowed disclosure and five mandated/recommended disclosure. The Islamic Organization for Medical Sciences code was silent on both issues.ConclusionCodes regarding disclosure of terminal illness to patients and families differed markedly among Islamic countries. They were silent in one-third of the codes, and tended to favour a paternalistic/utilitarian, family-centred approach over an autonomous, patient-centred approach.
Prevalence of antimicrobial‐resistant Escherichia coli in dogs in a cross‐sectional, community‐based study
Authors: Wedley A. L. , Maddox T. W. , Westgarth C. , Coyne K. P. , Pinchbeck G. L. , Williams N. J. , Dawson S. 
Published: March 2011

The prevalence of carriage of antimicrobial‐resistant (AMR) and extended‐spectrum β‐lactamase (ESBL)‐producing Escherichia coli was determined in 183 healthy dogs from a semi‐rural community in Cheshire. Isolates were tested against a panel of antimicrobials and by PCR to detect resistance genes. In the suspected ESBL‐producing isolates, the presence of bla SHV, bla TEM, bla CTX‐M and bla AmpC genes was determined by PCR and sequencing. A total of 53 (29 per cent, 95 per cent confidence interval [CI] 22.4 to 35.5 per cent) dogs carried at least one AMR E coli isolate. Twenty‐four per cent (95 per cent CI 17.9 to 30.2 per cent) of dogs carried isolates resistant to ampicillin, 19.7 per cent (95 per cent CI 13.9 to 25.4 per cent) to tetracycline and 16.9 per cent (95 per cent CI 11.5 to 22.4 per cent) to trimethoprim. A bla TEM gene was detected in 39 of 54 ampicillin‐resistant isolates, a tet(B) gene in 12 of 45 tetracycline‐resistant isolates, and a dfr gene in 22 of 33 trimethoprim‐resistant isolates. Multidrug‐resistant isolates were demonstrated in 15 per cent (28 of 183; 95 per cent CI 10.1 to 20.5 per cent) of dogs. Nine suspected ESBL‐producing E coli were isolated, of which only one was confirmed by double disc diffusion testing. Two of these isolates carried the bla TEM‐1 gene and seven carried the bla CMY‐2 gene.
LIFTING THEOREMS FOR TENSOR FUNCTORS ON MODULE CATEGORIES
Authors: WISBAUER ROBERT 
Published: March 2011

Any (co)ring R is an endofunctor with (co)multiplication on the category of abelian groups. These notions were generalized to monads and comonads on arbitrary categories. Starting around 1970 with papers by Beck, Barr and others a rich theory of the interplay between such endofunctors was elaborated based on distributive laws between them and Applegate's lifting theorem of functors between categories to related (co)module categories. Curiously enough some of these results were not noticed by researchers in module theory and thus notions like entwining structures and smash products between algebras and coalgebras were introduced (in the nineties) without being aware that these are special cases of the more general theory. The purpose of this survey is to explain several of these notions and recent results from general category theory in the language of elementary module theory focusing on functors between module categories given by tensoring with a bimodule. This provides a simple and systematic approach to smash products, wreath products, corings and rings over corings (C-rings). We also highlight the relevance of the Yang–Baxter equation for the structures on the threefold tensor product of algebras or coalgebras (see 3.6).
PLONGEMENTS LOCAUX ET EXTENSIONS DE CORPS DE NOMBRES
Authors: MAIRE CHRISTIAN 
Published: March 2011

Dans ce travail, nous nous intéressons au plongement [Formula: see text] des T-unités d'un corps de nombres K dans une partie de ses complétés p-adiques construite sur l'ensemble S. Nous montrons que l'injectivité de [Formula: see text] permet d'obtenir des informations sur la structure du groupe de Galois de certaines extensions de K où la ramification est liée à S et la décomposition à T. Nous étudions également le comportement asymptotique du noyau de [Formula: see text] le long d'une extension p-adique analytique sans p-torsion. In this article, we are interested in the embedding [Formula: see text] of the T-units of a number field K in some part of its p-adic completions at S. We show that the injectivity of [Formula: see text] allows us to obtain some information on the structure of the Galois group of some extensions of K where the ramification is attached at S and the decomposition at T. Moreover, we study the asymptotic behavior of the kernel [Formula: see text] along a p-adic analytic extension.
CONOYAUX DE CAPITULATION ET MODULES D'IWASAWA
Authors: PITOUN FRÉDÉRIC 
Published: March 2011

Soit F un corps de nombres totalement réel et p un premier impair, on note K0 = F(ζp). Pour n ∈ ℕ, Kn désigne le n-ième étage de la ℤp-extension cyclotomique K∞/K0, An est la p-partie du groupe des classes de Kn, [Formula: see text] et N∞ est l'extension de K∞ obtenue en extrayant des racines p-primaires d'unités. Le but de cet article est de montrer que le dual de Pontryagin de la partie plus des conoyaux de capitulation [Formula: see text], sur laquelle l'action de Γ a été tordue une fois par le caractère cyclotomique et la partie moins de la ℤp-torsion du groupe de Galois Gal (N∞ ∩ L∞/K∞) sont isomorphes. Let F be a totally real number field and p an odd prime, we note K0 = F(ζp). For an integer n, Kn is the nth floor of the ℤp-cyclotomic extension K∞/K0, An is the p-part of the class group of Kn, [Formula: see text] and N∞ is the extension of K∞ generated by p-primary roots of units. In this article, we prove that the plus part of the capitulation's cokernel [Formula: see text], on which Γ-action was twisted on time by the cyclotomic character, and the minus part of the ℤp-torsion of the Galois group Gal (N∞ ∩ L∞/K∞) is isomorphic.
Generalized Hyers-Ulam Stability of the Pexiderized Cauchy Functional Equation in Non-Archimedean Spaces
Authors: Najati Abbas , Cho YeolJe 
Published: March 2011

AbstractWe prove the generalized Hyers-Ulam stability of the Pexiderized Cauchy functional equation "Equation missing" in non-Archimedean spaces.
Common Fixed Point Theorems for a Finite Family of Discontinuous and Noncommutative Maps
Authors: Lin Lai-Jiu , Wang Sung-Yu 
Published: March 2011

AbstractWe study common fixed point theorems for a finite family of discontinuous and noncommutative single-valued functions defined in complete metric spaces. We also study a common fixed point theorem for two multivalued self-mappings and a stationary point theorem in complete metric spaces. Throughout this paper, we establish common fixed point theorems without commuting and continuity assumptions. In contrast, commuting or continuity assumptions are often assumed in common fixed point theorems. We also give examples to show our results. Results in this paper except those that generalized Banach contraction principle and those improve and generalize recent results in fixed point theorem are original and different from any existence result in the literature. The results in this paper will have some applications in nonlinear analysis and fixed point theory.
Molecular Classification of Gastric Cancer: A New Paradigm
Authors: Shah Manish A. , Khanin Raya , Tang Laura , Janjigian Yelena Y. , Klimstra David S. , Gerdes Hans , Kelsen David P. 
Published: March 2011

Abstract
Purpose: Gastric cancer may be subdivided into 3 distinct subtypes—proximal, diffuse, and distal gastric cancer—based on histopathologic and anatomic criteria. Each subtype is associated with unique epidemiology. Our aim is to test the hypothesis that these distinct gastric cancer subtypes may also be distinguished by gene expression analysis.
Experimental Design: Patients with localized gastric adenocarcinoma being screened for a phase II preoperative clinical trial (National Cancer Institute, NCI #5917) underwent endoscopic biopsy for fresh tumor procurement. Four to 6 targeted biopsies of the primary tumor were obtained. Macrodissection was carried out to ensure more than 80% carcinoma in the sample. HG-U133A GeneChip (Affymetrix) was used for cDNA expression analysis, and all arrays were processed and analyzed using the Bioconductor R-package.
Results: Between November 2003 and January 2006, 57 patients were screened to identify 36 patients with localized gastric cancer who had adequate RNA for expression analysis. Using supervised analysis, we built a classifier to distinguish the 3 gastric cancer subtypes, successfully classifying each into tightly grouped clusters. Leave-one-out cross-validation error was 0.14, suggesting that more than 85% of samples were classified correctly. Gene set analysis with the false discovery rate set at 0.25 identified several pathways that were differentially regulated when comparing each gastric cancer subtype to adjacent normal stomach.
Conclusions: Subtypes of gastric cancer that have epidemiologic and histologic distinctions are also distinguished by gene expression data. These preliminary data suggest a new classification of gastric cancer with implications for improving our understanding of disease biology and identification of unique molecular drivers for each gastric cancer subtype. Clin Cancer Res; 17(9); 2693–701. ©2011 AACR.