bluuebunny/crossref_metadata_2025 huggingface dataset:
Mixed Infection with Beijing and Non-Beijing Strains and Drug Resistance Pattern of
Mycobacterium tuberculosis
Authors: Huang Han-Yu , Tsai Yau-Sheng , Lee Jen-Jeh , Chiang Man-Chin , Chen Ying-Huei , Chiang Chen-Yuan , Lin Nien-Tsung , Tsai Pei-Jane
Published: October 2010

Mixed infection with Beijing and non-Beijing strains of
Mycobacterium tuberculosis
has been reported and has been suggested to mediate elevation of the reinfection rate in regions with a high incidence of tuberculosis (TB). To evaluate the prevalence of infection with both Beijing and non-Beijing strains of
M. tuberculosis
in eastern Taiwan, the region with the highest TB incidence in Taiwan, 185 active pulmonary TB patients were enrolled at Tzu Chi General Hospital from October 2007 to September 2008. A modified multiplex PCR method was developed to distinguish Beijing and non-Beijing strains directly using the sputum of patients. Of the 185 patients, 46.5% were infected with a Beijing strain, 42.2% were infected with a non-Beijing strain, and 11.3% were infected with both strain types. Notably, mixed infection with both strain types was not associated with TB treatment history or the high-incidence race group, aborigines. In addition, the incidence rate of mixed infection before treatment with anti-TB medication was as high as that in patients with a history of anti-TB treatment. Further analysis of antibiotic susceptibility revealed that Beijing strains alone had the highest multidrug resistance rate (17.5%), mixed infection had the highest rate of resistance to at least one drug (23.8%), and non-Beijing strains had the highest rate of sensitivity to all drugs (79.5%), implying that Beijing strains are predominant in the development of drug resistance in tuberculosis.
Screening for
Acinetobacter baumannii
Colonization by Use of Sponges
Authors: Doi Yohei , Onuoha Ezenwa O. , Adams-Haduch Jennifer M. , Pakstis Diana L. , McGaha Traci L. , Werner Carly A. , Parker Bridget N. , Brooks Maria M. , Shutt Kathleen A. , Pasculle Anthony W. , Muto Carlene A. , Harrison Lee H.
Published: October 2010

There is currently no consensus method for the active screening of
Acinetobacter baumannii
. The use of swabs to culture nostrils, pharynx, and skin surface of various anatomical sites is known to yield less-than-optimal sensitivity. In the present study, we sought to determine whether the use of sterile sponges to sample large areas of the skin would improve the sensitivity of the detection of
A. baumannii
colonization. Forty-six patients known to be colonized with
A. baumannii
, defined by a positive clinical culture for this organism as defined by resistance to more than two classes of antimicrobials, participated in the study. The screening sites included the forehead, nostrils, buccal mucosa, axilla, antecubital fossa, groin, and toe webs with separate rayon swabs and the forehead, upper arm, and thigh with separate sponges. Modified Leeds Acinetobacter medium (mLAM) agar plates that contained vancomycin and either aztreonam or ceftazidime were used as the selective medium. An enrichment culture grown overnight substantially increased the sensitivity for most sites. The sensitivity ranged between 69.6 and 82.6% for individual sponge sites and 21.7 to 52.2% for individual swab sites when mLAM plates with ceftazidime were inoculated after a 24-h enrichment period. The sponge and swab sites with the best sensitivity were the leg and the buccal mucosa, respectively (82.6% and 52.2%;
P
= 0.003). The combined sensitivity for the upper arm and leg with a sponge was 89.1%. The novel screening method using sterile sponges was easy to perform and achieved excellent sensitivity for the detection of
A. baumannii
colonization.
Genotyping of
Enterococcus faecalis
and
Enterococcus faecium
Isolates by Use of a Set of Eight Single Nucleotide Polymorphisms
Authors: Rathnayake I. U. , Hargreaves M. , Huygens F.
Published: October 2010

A single nucleotide polymorphism (SNP) genotyping method for
Enterococcus faecalis
and
Enterococcus faecium
was developed using the “Minimum SNPs” program. SNP sets were interrogated using allele-specific real-time PCR. SNP typing subdivided clonal complexes 2 and 9 of
E. faecalis
and 17 of
E. faecium
, members of which cause the majority of nosocomial infections globally.
Enteric Fever in a 6-Year-Old Traveler Caused by
Salmonella enterica
Serotypes Typhi and Paratyphi A: Laboratory Detection Strategies and Treatment Options
Authors: Humphries Romney M. , Yeganeh Nava , Ward Kevin W. , Lewinski M. A. , Ching Natascha
Published: October 2010

We report the first pediatric case of enteric fever caused by
Salmonella enterica
serotypes Typhi and Paratyphi A. Mixed infections are infrequently reported, potentially because detection of two different
Salmonella
serotypes in blood cultures is technically challenging. We suggest laboratory strategies to aid in the recognition of mixed infections.
Identification by Genotyping of a Commercial Antigen Preparation as the Source of a Laboratory Contamination with
Coxiella burnetii
and as an Unexpected Rich Source of Control DNA
Authors: Tilburg Jeroen J. H. C. , Horrevorts Alphons M. , Peeters Marcel F. , Klaassen Corné H. W. , Rossen John W. A.
Published: October 2010

By performing genotyping, a laboratory contamination involving Q fever was traced back to the antigen preparation used in a commercially available complement fixation test. It was established that such antigen preparations contain relatively high loads of DNA/RNA, making them potential sources of contamination but also convenient preparations for control material.
Quantitative Detection of Enterotoxigenic
Bacteroides fragilis
Subtypes Isolated from Children with and without Diarrhea
Authors: Merino V. R. C. , Nakano V. , Liu C. , Song Y. , Finegold S. M. , Avila-Campos M. J.
Published: October 2010

A rapid real-time PCR (RT-PCR) approach was developed to detect the
bft
gene subtypes in
Bacteroides fragilis
isolated from fecal samples. DNA obtained from diarrhea (110) and nondiarrhea (150) samples was evaluated. Subtype 1 was observed in 9 (8.2%) diarrhea and 7 (4.7%) nondiarrhea samples. Subtype 2 was not detected in any DNA samples, and subtype 3 was observed in only 1 diarrhea sample. The presence of the
bft-1
gene did not show any statistically significant differences between the groups of children. This technique could be used to evaluate a possible correlation between disease and the presence of
B. fragilis
enterotoxin.
Development and Evaluation of a Rapid Influenza Diagnostic Test for the Pandemic (H1N1) 2009 Influenza Virus
Authors: Kwon Donghyok , Shin Kyeongcheol , Kwon Mihwa , Oh Hee-Bok , Kang Chun , Lee Joo-Yeon
Published: October 2010

We evaluated a new rapid influenza diagnostic test for the pandemic (H1N1) 2009 influenza virus by using real-time reverse transcription-PCR (rRT-PCR) and viral culture. The sensitivities were 68.5% and 64.5%, and the specificities were 98.4% and 97.6%, respectively. This kit should be used with caution, and negative results should be verified by a confirmative test.
Intrafamilial Cluster of Pulmonary Tuberculosis Due to
Mycobacterium bovis
of the African 1 Clonal Complex
Authors: Godreuil S. , Jeziorski E. , Bañuls A. L. , Fraisse T. , Van de Perre P. , Boschiroli M. L.
Published: October 2010

A new clonal complex of
Mycobacterium bovis
present at high frequency in cattle from west central African countries has been described as the African 1 (Af1) clonal complex. Here, the first intrafamilial cluster of human tuberculosis cases due to
M. bovis
Af1 clonal complex strains is reported. We discuss hypotheses regarding modes of transmission.
Temporal Characterization of Carrot Broth-Enhanced Real-Time PCR as an Alternative Means for Rapid Detection of
Streptococcus agalactiae
from Prenatal Anorectal and Vaginal Screenings
Authors: Munson Erik , Napierala Maureen , Munson Kimber L. , Culver Anne , Hryciuk Jeanne E.
Published: October 2010

Analysis of overnight carrot broth culture using the BD GeneOhm StrepB assay (carrot broth-enhanced PCR) yields increased sensitivity compared to that of carrot broth culture alone for the detection of
Streptococcus agalactiae
. We investigated the prospect of reducing the carrot broth incubation time prior to PCR performance.
In vitro
experimentation demonstrated that carrot broth-enhanced PCR nominally detected 10 CFU
S. agalactiae
after 4 h of carrot broth incubation with competitive flora. Detection rates improved with inocula of 100 and 1,000 CFU
S. agalactiae
, with the majority of these aliquots demonstrating detection after 2 h of carrot broth incubation. Carrot broth was prospectively inoculated with clinical vaginal/anorectal swabs, with 500-μl aliquots collected. Early aliquots from 227 specimens were subjected to carrot broth-enhanced PCR (early-aliquot carrot broth-enhanced PCR) in instances of subsequent positive carrot broth culture or positive overnight clinical carrot broth-enhanced PCR. The
S. agalactiae
detection rate by early-aliquot carrot broth-enhanced PCR (66.1%) exceeded that observed for 227 remnant swabs retrospectively tested by direct swab PCR (56.4%;
P
= 0.03). Early-aliquot carrot broth-enhanced PCR detection rate differences were most pronounced in aliquots from 83 carrot broth aliquots collected after 6 h (84.3%) compared to detection rates from either direct swab PCR of these samples (51.8%;
P
< 0.0002) or early-aliquot carrot broth-enhanced PCR of 144 carrot broth aliquots collected after fewer than 6 h of incubation (55.6%;
P
< 0.0002). Enhanced sensitivity of early-aliquot carrot broth-enhanced PCR versus direct swab PCR suggests that this assay could serve as a surrogate rapid detection method facilitating the prevention of group B streptococcal disease.
A Nuclear Inhibitor of NF-κB Encoded by a Poxvirus
Authors: Diel D. G. , Luo S. , Delhon G. , Peng Y. , Flores E. F. , Rock D. L.
Published: October 2010

Poxviruses have evolved various strategies to inhibit cytoplasmic events leading to activation of the nuclear factor κB (NF-κB) signaling pathway, with individual viruses often encoding multiple NF-κB inhibitors. Here, the novel orf virus (ORFV)-encoded protein ORFV002 was shown to inhibit nuclear events regulating NF-κB transcriptional activity. ORFV002 expression in cell cultures significantly decreased wild-type-virus-, tumor necrosis factor alpha (TNF-α)-, and lipopolysaccharide (LPS)-induced NF-κB-mediated gene expression. Expression of ORFV002 in cells, while not affecting phosphorylation or nuclear translocation of NF-κB-p65, markedly decreased TNF-α- and wild-type-virus-induced acetylation of NF-κB-p65, a p300-mediated nuclear modification of NF-κB-p65 that regulates its transactivating activity. ORFV002 was shown to colocalize and interact with NF-κB-p65, and expression of ORFV002 in cell cultures resulted in a reduced interaction of NF-κB-p65 with p300, suggesting that ORFV002 interferes with NF-κB-p65/p300 association. Deletion of
ORFV002
from the OV-IA82 genome had no significant effect on ORFV pathogenesis in sheep, indicating that
ORFV002
is nonessential for virus virulence in the natural host. This represents the first description of a nuclear inhibitor of NF-κB encoded by a poxvirus.
Adenovirus Membrane Penetration Activates the NLRP3 Inflammasome
Authors: Barlan A. U. , Griffin T. M. , Mcguire K. A. , Wiethoff C. M.
Published: October 2010

Adenovirus type 5 (Ad5) infection of macrophages results in rapid secretion of interleukin-1β (IL-1β) and is dependent on the inflammasome components NLRP3 and ASC and the catalytic activity of caspase-1. Using lentivirus-expressed short hairpin RNA (shRNA) and competitive inhibitors, we show that Ad-induced IL-1β release is dependent upon Toll-like receptor 9 (TLR9) sensing of the Ad5 double-stranded DNA (dsDNA) genome in human cell lines and primary monocyte-derived macrophages but not in mouse macrophages. Additionally, a temperature-sensitive mutant of Ad5 unable to penetrate endosomal membranes,ts1, is unable to induce IL-1β release in TLR2-primed THP-1 cells, suggesting that penetration of endosomal membranes is required for IL-1β release. Disruption of lysosomal membranes and the release of cathepsin B into the cytoplasm are required for Ad-induced NLRP3 activation. Ad5 cell entry also induces reactive oxygen species (ROS) production, and inhibitors of ROS prevent Ad-induced IL-1β release. Ad5 activation of NLRP3 also induces necrotic cell death, resulting in the release of the proinflammatory molecule HMGB1. This work further defines the mechanisms of virally induced inflammasome activation.
Characterization of Cross-Reactive CD8
+
T-Cell Recognition of HLA-A2-Restricted HIV-Gag (SLYNTVATL) and HCV-NS5b (ALYDVVSKL) Epitopes in Individuals Infected with Human Immunodeficiency and Hepatitis C Viruses
Authors: Vali Bahareh , Tohn Robert , Cohen Michael J. , Sakhdari Ali , Sheth Prameet M. , Yue Feng Yun , Wong David , Kovacs Colin , Kaul Rupert , Ostrowski Mario A.
Published: October 2010

The immunologic mechanisms underlying the faster progression of hepatitis C virus (HCV) disease in the presence of human immunodeficiency virus (HIV) coinfection are not clearly understood. T-cell cross-reactivity between HCV and influenza virus-specific epitopes has been associated with rapid progression of HCV disease (S. Urbani, B. Amadei, P. Fisicaro, M. Pilli, G. Missale, A. Bertoletti, and C. Ferrari, J. Exp. Med. 201:675-680, 2005). We asked whether T-cell cross-reactivity between HCV and HIV could exist during HCV/HIV coinfection and affect pathogenesis. Our search for amino acid sequence homology between the HCV and HIV proteomes revealed two similar HLA-A2-restricted epitopes, HIV-Gag (SLYNTVATL [HIV-SL9]) and HCV-NS5b (ALYDVVSKL [HCV-AL9]). We found that 4 out of 20 HLA-A2-positive (HLA-A2
+
) HIV-infected individuals had CD8
+
T cells that recognized both the HIV-SL9 and HCV-AL9 epitopes. However, the AL9 epitope was generally shown to be a weak agonist. Although HCV-monoinfected individuals in our study did not show AL9-specific responses, we found that about half of HCV/HIV-coinfected individuals had dual responses to both epitopes. High dual T-cell recognition among coinfected subjects was usually due to separate T-cell populations targeting each epitope, as determined by pentamer staining. The one individual demonstrating cross-reactive T cells to both epitopes showed the most advanced degree of liver disease. In coinfected individuals, we observed a positive correlation between the magnitudes of T-cell responses to both the SL9 and the AL9 epitopes, which was also positively associated with the clinical parameter of liver damage. Thus, we find that HIV infection induces T cells that can cross-react to heterologous viruses or prime for T cells that are closely related in sequence. However, the induction of cross-reactive T cells may not be associated with control of disease caused by the heterologous virus. This demonstrates that degeneracy of HIV-specific T cells may play a role in the immunopathology of HCV/HIV coinfection.
Template Recognition Mechanisms by Replicase Proteins Differ between Bipartite Positive-Strand Genomic RNAs of a Plant Virus
Authors: Iwakawa Hiro-oki , Mine Akira , Hyodo Kiwamu , An Mengnan , Kaido Masanori , Mise Kazuyuki , Okuno Tetsuro
Published: October 2010

Recognition of RNA templates by viral replicase proteins is one of the key steps in the replication process of all RNA viruses. However, the mechanisms underlying this phenomenon, including primary RNA elements that are recognized by the viral replicase proteins, are not well understood. Here, we used aptamer pulldown assays with membrane fractionation and protein-RNA coimmunoprecipitation in a cell-free viral translation/replication system to investigate how viral replicase proteins recognize the bipartite genomic RNAs of theRed clover necrotic mosaic virus(RCNMV). RCNMV replicase proteins bound specifically to a Y-shaped RNA element (YRE) located in the 3′ untranslated region (UTR) of RNA2, which also interacted with the 480-kDa replicase complexes that contain viral and host proteins. The replicase-YRE interaction recruited RNA2 to the membrane fraction. Conversely, RNA1 fragments failed to interact with the replicase proteins supplied intrans. The results of protein-RNA coimmunoprecipitation assays suggest that RNA1 interacts with the replicase proteins coupled with their translation. Thus, the initial template recognition mechanisms employed by the replicase differ between RCNMV bipartite genomic RNAs and RNA elements are primary determinants of the differential replication mechanism.
Serine-Threonine Ubiquitination Mediates Downregulation of BST-2/Tetherin and Relief of Restricted Virion Release by HIV-1 Vpu
Authors: Tokarev Andrey A. , Munguia Jason , Guatelli John C.
Published: October 2010

The HIV-1 protein Vpu counteracts the antiviral activity of the innate restriction factor BST-2/tetherin by a mechanism that partly depends on its interaction with β-TrCP, a substrate adaptor for an SCF (Skp-Cullin 1-F box) E3 ubiquitin ligase complex. This suggests that Vpu stimulates the ubiquitination of BST-2 and that this underlies the relief of restriction. Here, we show that Vpu stimulates ubiquitination of BST-2. Mutation of all potential ubiquitination sites in the cytoplasmic domain of BST-2, including lysines, cysteines, serines, and threonines, abrogates Vpu-mediated ubiquitination. However, a serine-threonine-serine sequence specifically mediates the downregulation of BST-2 from the cell surface and the optimal relief of restricted virion release. Serine-threonine ubiquitination of BST-2 is likely part of the mechanism by which Vpu counteracts innate defenses.
Association of TRIM22 with the Type 1 Interferon Response and Viral Control during Primary HIV-1 Infection
Authors: Singh Ravesh , Gaiha Gaurav , Werner Lise , McKim Kevin , Mlisana Koleka , Luban Jeremy , Walker Bruce D. , Karim Salim S. Abdool , Brass Abraham L. , Ndung'u Thumbi
Published: October 2010

Type 1 interferons (IFNs) induce the expression of the tripartite interaction motif (TRIM) family of E3 ligases, but the contribution of these antiviral factors to HIV pathogenesis is not completely understood. We hypothesized that the increased expression of select type 1 IFN and TRIM isoforms is associated with a significantly lower likelihood of HIV-1 acquisition and viral control during primary HIV-1 infection. We measured IFN-α, IFN-β, myxovirus resistance protein A (MxA), human TRIM5α (huTRIM5α), and TRIM22 mRNA levels in peripheral blood mononuclear cells (PBMCs) of high-risk, HIV-1-uninfected participants and HIV-1-positive study participants. Samples were available for 32 uninfected subjects and 28 infected persons, all within 1 year of infection. HIV-1-positive participants had higher levels of IFN-β (
P
= 0.0005), MxA (
P
= 0.007), and TRIM22 (
P
= 0.01) and lower levels of huTRIM5α (
P
< 0.001) than did HIV-1-negative participants. TRIM22 but not huTRIM5α correlated positively with type 1 IFN (IFN-α, IFN-β, and MxA) (all
P
< 0.0001). In a multivariate model, increased MxA expression showed a significant positive association with viral load (
P
= 0.0418). Furthermore, TRIM22 but not huTRIM5α, IFN-α, IFN-β, or MxA showed a negative correlation with plasma viral load (
P
= 0.0307) and a positive correlation with CD4
+
T-cell counts (
P
= 0.0281).
In vitro
studies revealed that HIV infection induced TRIM22 expression in PBMCs obtained from HIV-negative donors. Stable TRIM22 knockdown resulted in increased HIV-1 particle release and replication in Jurkat reporter cells. Collectively, these data suggest concordance between type 1 IFN and TRIM22 but not huTRIM5α expression in PBMCs and that TRIM22 likely acts as an antiviral effector
in vivo
.
T Cell-Mediated Protection against Lethal 2009 Pandemic H1N1 Influenza Virus Infection in a Mouse Model
Authors: Guo Hailong , Santiago Félix , Lambert Kris , Takimoto Toru , Topham David J.
Published: October 2010

Genetic mutation and reassortment of influenza virus gene segments, in particular those of hemagglutinin (HA) and neuraminidase (NA), that lead to antigenic drift and shift are the major strategies for influenza virus to escape preexisting immunity. The most recent example of such phenomena is the first pandemic of H1N1 influenza of the 21st century, which started in 2009. Cross-reactive antibodies raised against H1N1 viruses circulating before 1930 show protective activity against the 2009 pandemic virus. Cross-reactive T-cell responses can also contribute to protection, butin vivosupport of this view is lacking. To explore the protection mechanismsin vivo, we primed mice with H1 and H3 influenza virus isolates and rechallenged them with a virus derived from the 2009 H1N1 A/CA/04/09 virus, named CA/E3/09. We found that priming with influenza viruses of both H1 and H3 homo- and heterosubtypes protected against lethal CA/E3/09 virus challenge. Convalescent-phase sera from these primed mice conferred no neutralization activityin vitroand no protectionin vivo. However, T-cell depletion studies suggested that both CD4 and CD8 T cells contributed to the protection. Taken together, these results indicate that cross-reactive T cells established after initial priming with distally related viruses can be a vital component for prevention of disease and control of pandemic H1N1 influenza virus infection. Our results highlight the importance of establishing cross-reactive T-cell responses for protecting against existing or newly emerging pandemic influenza viruses.
Upregulation of CXCL10 in Human Dorsal Root Ganglia during Experimental and Natural Varicella-Zoster Virus Infection
Authors: Steain Megan , Gowrishankar Kavitha , Rodriguez Michael , Slobedman Barry , Abendroth Allison
Published: October 2010

Varicella-zoster virus (VZV) reactivation causes herpes zoster, which is accompanied by an influx of lymphocytes into affected ganglia, but the stimulus for this infiltrate is not known. We report that VZV infection of ganglia leads to increased CXCL10 production
in vitro
, in an explant ganglion model and in naturally infected dorsal root ganglia (DRG) during herpes zoster. Lymphocytes expressing the receptor for CXCL10, CXCR3, were also observed throughout naturally infected ganglia during herpes zoster, including immediately adjacent to neurons. This study identifies VZV-induced CXCL10 as a potential driver of T lymphocyte recruitment into DRG during herpes zoster.
An In-Depth Analysis of Original Antigenic Sin in Dengue Virus Infection
Authors: Midgley Claire M. , Bajwa-Joseph Martha , Vasanawathana Sirijitt , Limpitikul Wannee , Wills Bridget , Flanagan Aleksandra , Waiyaiya Emily , Tran Hai Bac , Cowper Alison E. , Chotiyarnwon Pojchong , Grimes Jonathan M. , Yoksan Sutee , Malasit Prida , Simmons Cameron P. , Mongkolsapaya Juthathip , Screaton Gavin R.
Published: October 2010

The evolution of dengue viruses has resulted in four antigenically similar yet distinct serotypes. Infection with one serotype likely elicits lifelong immunity to that serotype, but generally not against the other three. Secondary or sequential infections are common, as multiple viral serotypes frequently cocirculate. Dengue infection, although frequently mild, can lead to dengue hemorrhagic fever (DHF) which can be life threatening. DHF is more common in secondary dengue infections, implying a role for the adaptive immune response in the disease. There is currently much effort toward the design and implementation of a dengue vaccine but these efforts are made more difficult by the challenge of inducing durable neutralizing immunity to all four viruses. Domain 3 of the dengue virus envelope protein (ED3) has been suggested as one such candidate because it contains neutralizing epitopes and it was originally thought that relatively few cross-reactive antibodies are directed to this domain. In this study, we performed a detailed analysis of the anti-ED3 response in a cohort of patients suffering either primary or secondary dengue infections. The results show dramatic evidence of original antigenic sin in secondary infections both in terms of binding and enhancement activity. This has important implications for dengue vaccine design because heterologous boosting is likely to maintain the immunological footprint of the first vaccination. On the basis of these findings, we propose a simplein vitroenzyme-linked immunosorbent assay (ELISA) to diagnose the original dengue infection in secondary dengue cases.
Reverse Genetics Generation of Chimeric Infectious Junin/Lassa Virus Is Dependent on Interaction of Homologous Glycoprotein Stable Signal Peptide and G2 Cytoplasmic Domains
Authors: Albariño César G. , Bird Brian H. , Chakrabarti Ayan K. , Dodd Kimberly A. , White David M. , Bergeron Éric , Shrivastava-Ranjan Punya , Nichol Stuart T.
Published: October 2010

The
Arenaviridae
are a diverse and globally distributed collection of viruses that are maintained primarily by rodent reservoirs. Junin virus (JUNV) and Lassa virus (LASV) can both cause significant outbreaks of severe and often fatal human disease throughout their respective areas of endemicity. In an effort to improve upon the existing live attenuated JUNV Candid1 vaccine, we generated a genetically homogenous stock of this virus from cDNA copies of the virus S and L segments by using a reverse genetics system. Further, these cDNAs were used in combination with LASV cDNAs to successfully generate two recombinant Candid1 JUNV/LASV chimeric viruses (via envelope glycoprotein [GPC] exchange). It was found that while the GPC extravirion domains were readily exchangeable, homologous stable signal peptide (SSP) and G2 transmembrane and cytoplasmic tail domains were essential for correct GPC maturation and production of infectious chimeric viruses. The switching of the JUNV and LASV G1/G2 ectodomains within the Candid1 vaccine background did not alter the attenuated phenotype of the vaccine strain in a lethal mouse model. These recombinant chimeric viruses shed light on the fundamental requirements of arenavirus GPC maturation and may serve as a strategy for the development of bivalent JUNV and LASV vaccine candidates.
R5 HIV
env
and Vesicular Stomatitis Virus G Protein Cooperate To Mediate Fusion to Naïve CD4
+
T Cells
Authors: Pace Matthew J. , Agosto Luis , O'Doherty Una
Published: October 2010

Naïve CD4
4
T cells are resistant to both HIV R5
env
and vesicular stomatitis virus G protein (VSV-G)-mediated fusion. However, viral particles carrying both HIV R5
env
and VSV-G infect naïve cells by an unexplained mechanism. We show that VSV-G-pseudotyped virus cannot fuse to unstimulated cells because the viral particles cannot be endocytosed. However, virions carrying both HIV R5
env
and VSV-G can fuse because CD4 binding allows viral uptake. Our findings reveal a unique mechanism by which R5 HIV
env
and VSV-G cooperate to allow entry to naïve CD4
+
T cells, providing a tool to target naïve CD4
+
T cells with R5 HIV to study HIV coreceptor signaling and latency.
Assembly and Immunological Properties of Newcastle Disease Virus-Like Particles Containing the Respiratory Syncytial Virus F and G Proteins
Authors: McGinnes Lori W. , Gravel Kathryn A. , Finberg Robert W. , Kurt-Jones Evelyn A. , Massare Michael J. , Smith Gale , Schmidt Madelyn R. , Morrison Trudy G.
Published: October 2010

Human respiratory syncytial virus (RSV) is a serious respiratory pathogen in infants and young children as well as elderly and immunocompromised populations. However, no RSV vaccines are available. We have explored the potential of virus-like particles (VLPs) as an RSV vaccine candidate. VLPs composed entirely of RSV proteins were produced at levels inadequate for their preparation as immunogens. However, VLPs composed of the Newcastle disease virus (NDV) nucleocapsid and membrane proteins and chimera proteins containing the ectodomains of RSV F and G proteins fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, were quantitatively prepared from avian cells. Immunization of mice with these VLPs, without adjuvant, stimulated robust, anti-RSV F and G protein antibody responses. IgG2a/IgG1 ratios were very high, suggesting predominantly T
H
1 responses. In contrast to infectious RSV immunization, neutralization antibody titers were robust and stable for 4 months. Immunization with a single dose of VLPs resulted in the complete protection of mice from RSV replication in lungs. Upon RSV intranasal challenge of VLP-immunized mice, no enhanced lung pathology was observed, in contrast to the pathology observed in mice immunized with formalin-inactivated RSV. These results suggest that these VLPs are effective RSV vaccines in mice, in contrast to other nonreplicating RSV vaccine candidates.
Cytomegalovirus MicroRNA Expression Is Tissue Specific and Is Associated with Persistence
Authors: Meyer Christine , Grey Finn , Kreklywich Craig N. , Andoh Takeshi F. , Tirabassi Rebecca S. , Orloff Susan L. , Streblow Daniel N.
Published: October 2010

MicroRNAs (miRNAs) are a class of small noncoding RNAs involved in posttranscriptional regulation. miRNAs are utilized in organisms ranging from plants to higher mammals, and data have shown that DNA viruses also use this method for host and viral gene regulation. Here, we report the sequencing of the small RNAs in rat cytomegalovirus (RCMV)-infected fibroblasts and persistently infected salivary glands. We identified 24 unique miRNAs that mapped to hairpin structures found within the viral genome. While most miRNAs were detected in both samples, four were detected exclusively in the infected fibroblasts and two were specific for the infected salivary glands. The RCMV miRNAs are distributed across the viral genome on both the positive and negative strands, with clusters of miRNAs at a number of locations, including near viral genesr1andr111. The RCMV miRNAs have a genomic positional orientation similar to that of the miRNAs described for mouse cytomegalovirus, but they do not share any substantial sequence conservation. Similar to other reported miRNAs, the RCMV miRNAs had considerable variation at their 3′ and 5′ ends. Interestingly, we found a number of specific examples of differential isoform usage between the fibroblast and salivary gland samples. We determined by real-time PCR that expression of the RCMV miRNA miR-r111.1-2 is highly expressed in the salivary glands and that miR-R87-1 is expressed in most tissues during the acute infection phase. Our study identified the miRNAs expressed by RCMVin vitroandin vivoand demonstrated that expression is tissue specific and associated with a stage of viral infection.
Reovirus Infection or Ectopic Expression of Outer Capsid Protein μ1 Induces Apoptosis Independently of the Cellular Proapoptotic Proteins Bax and Bak
Authors: Wisniewski Meagan L. , Werner Brenda G. , Hom Louis G. , Anguish Lynne J. , Coffey Caroline M. , Parker John S. L.
Published: October 2010

Mammalian orthoreoviruses induce apoptosis
in vivo
and
in vitro
; however, the specific mechanism by which apoptosis is induced is not fully understood. Recent studies have indicated that the reovirus outer capsid protein μ1 is the primary determinant of reovirus-induced apoptosis. Ectopically expressed μ1 induces apoptosis and localizes to intracellular membranes. Here we report that ectopic expression of μ1 activated both the extrinsic and intrinsic apoptotic pathways with activation of initiator caspases-8 and -9 and downstream effector caspase-3. Activation of both pathways was required for μ1-induced apoptosis, as specific inhibition of either caspase-8 or caspase-9 abolished downstream effector caspase-3 activation. Similar to reovirus infection, ectopic expression of μ1 caused release into the cytosol of cytochrome
c
and smac/DIABLO from the mitochondrial intermembrane space. Pancaspase inhibitors did not prevent cytochrome
c
release from cells expressing μ1, indicating that caspases were not required. Additionally, μ1- or reovirus-induced release of cytochrome
c
occurred efficiently in Bax
−/−
Bak
−/−
mouse embryonic fibroblasts (MEFs). Finally, we found that reovirus-induced apoptosis occurred in Bax
−/−
Bak
−/−
MEFs, indicating that reovirus-induced apoptosis occurs independently of the proapoptotic Bcl-2 family members Bax and Bak.
RNA Aptamers Directed to Human Immunodeficiency Virus Type 1 Gag Polyprotein Bind to the Matrix and Nucleocapsid Domains and Inhibit Virus Production
Authors: Ramalingam Dhivya , Duclair Sonald , Datta Siddhartha A. K. , Ellington Andrew , Rein Alan , Prasad Vinayaka R.
Published: October 2010

Gag orchestrates the assembly and release of human immunodeficiency virus type 1 (HIV-1) particles. We explored here the potential of anti-Gag RNA aptamers to inhibit HIV-1 replication.
In vitro
, RNA aptamers raised against an HIV-1 Gag protein, lacking the N-terminal myristate and the C-terminal p6 (DP6-Gag), could bind to matrix protein (MA), nucleocapsid protein (NC), or entire DP6-Gag protein. Upon cotransfection with pNL4-3.Luc molecular clone into 293T cells, six of the aptamers caused mild inhibition (2- to 3-fold) in the extracellular capsid levels, and one aptamer displayed 20-fold inhibition. The reduction was not due to a release defect but reflected Gag mRNA levels. We hypothesized that the aptamers influence genomic RNA levels via perturbation of specific Gag-genomic RNA interactions. Binding studies revealed that the “NC-binders” specifically compete with the packaging signal (ψ) of HIV-1 for binding to DP6-Gag. Therefore, we tested the ability of two NC-binders to inhibit viruses containing ψ-region deletions (ΔSL1 or ΔSL3) and found that the NC-binders were no longer able to inhibit Gag synthesis. The inability of these aptamers to inhibit ψ-deleted viruses correlated with the absence of competition with the corresponding ψ transcripts lacking SL1 or SL3 for binding DP6-Gag
in vitro
. These results indicate that the NC-binding aptamers disrupt Gag-genomic RNA interaction and negatively affect genomic RNA transcription, processing, or stability. Our results reveal an essential interaction between HIV-1 Gag and the ψ-region that may be distinct from that which occurs during the encapsidation of genomic RNA. Thus, anti-Gag aptamers can be an effective tool to perturb Gag-genomic RNA interactions.
Ocular adnexal marginal zone B cell lymphoma infiltrated by IgG4-positive plasma cells
Authors: Kubota Toshinobu , Moritani Suzuko , Yoshino Tadashi , Nagai Hirokazu , Terasaki Hiroko
Published: October 2010

Aims

To report the clinicopathological characteristics of patients with ocular adnexal marginal zone B cell lymphoma (MZBL) with IgG4-positive plasma cells.

Methods

114 biopsy samples of ocular adnexal MZBLs were analysed. MZBLs with IgG4-positive plasma cells were included when the IgG4:IgG ratio was >40% (IgG4-related group). The serum levels of each subclass of immunoglobulins and soluble interleukin-2 receptor in the IgG4-related group were compared with those in 61 consecutive patients having MZBL without IgG4-positive plasma cells (IgG4-unrelated group). They were also compared with those in 10 patients having ocular adnexal IgG4-related lymphoplasmacytic disorder (IgG4-related inflammatory group).

Results

Ten (9%) of the patients were diagnosed with MZBL with IgG4-positive plasma cells. The IgG4-related group had a significantly greater degree of sclerosis and reactive follicles in the MZBLs (p=0.0004 and p=0.01, respectively). The serum levels of IgG, IgG1, IgG4, IgE and soluble interleukin 2 receptor in the IgG4-related group were significantly higher than those in the IgG4-unrelated group (p=0.003, p=0.009, p<0.0001, p<0.0001 and p=0.0007, respectively). The serum levels did not differ significantly from those of the IgG4-related inflammatory group. The IgG4-related group also had reactive IgG4-positive lymphoplasmacytic infiltrations in the recurrent lesion and in the stomach.

Conclusions

IgG4-positive plasma cells had infiltrated into ocular adnexal MZBLs in 9% of cases. It is suggested that ocular adnexal MZBLs with IgG4-positive plasma cells have unique histological and serological characteristics that overlap those of ocular adnexal IgG4-related lymphoplasmacytic infiltrative disorder and systemic conditions.
Urinary 8-hydroxy-2′-deoxyguanosine as a biomarker of oxidative DNA damage induced by ambient pollution in the Normative Aging Study
Authors: Ren Cizao , Fang Shona , Wright Robert O , Suh Helen , Schwartz Joel
Published: October 2010

Background

Studies show that exposure to air pollution damages human health, but the mechanisms are not fully understood. One suggested pathway is via oxidative stress.

Objectives

This study examines associations between exposure to air pollution and oxidative DNA damage, as indicated by urinary 8-hydroxy-2′-deoxyguanosine (8-OHdG) concentrations in ageing participants during 2006–2008.

Methods

We fit linear regression models to examine associations between air pollutants and 8-OHdG adjusting for potential confounders.

Results

8-OHdG was significantly associated with ambient particulate matter ≤2.5 μm in aerodynamic diameter (PM2.5), nitrogen dioxide (NO2), maximal 1 h ozone (O3), sulphate (SO42−) and organic carbon (OC), but not with black carbon (BC), carbon monoxide (CO), the number of particles (PN) or elemental carbon (EC). Effects were more apparent with multi-week averages of exposures. Per IQR increases in 21-day averages of PM2.5, PN, BC, EC, OC, CO, SO42−, NO2and maximal 1 h O3were associated with 30.8% (95% CI 9.3% to 52.2%), −13.1% (95% CI −41.7% to 15.5%), 3.0% (95% CI −19.8% to 25.8%), 5.3% (95% CI −23.6% to 34.2%), 24.4% (95% CI 1.8% to 47.1%), −2.0% (95% CI −12.4% to 8.3%), 29.8% (95% CI 6.3% to 53.3%), 32.2% (95% CI 7.4% to 56.9%) and 47.7% (95% CI 3.6% to 91.7%) changes in 8-OHdG, respectively.

Conclusions

This study suggests that ageing participants experienced an increased risk of developing oxidative DNA injury after exposure to secondary, but not primary, ambient pollutants.
CAN DISSIMILAR USERS CONTRIBUTE TO ACCURACY AND DIVERSITY OF PERSONALIZED RECOMMENDATION?
Authors: ZENG WEI , SHANG MING-SHENG , ZHANG QIAN-MING , LÜ LINYUAN , ZHOU TAO
Published: October 2010

Recommender systems are becoming a popular and important set of personalization techniques that assist individual users with navigating through the rapidly growing amount of information. A good recommender system should be able to not only find out the objects preferred by users, but also help users in discovering their personalized tastes. The former corresponds to high accuracy of the recommendation, while the latter to high diversity. A big challenge is to design an algorithm that provides both highly accurate and diverse recommendation. Traditional recommendation algorithms only take into account the contributions of similar users, thus, they tend to recommend popular items for users ignoring the diversity of recommendations. In this paper, we propose a recommendation algorithm by considering both the effects of similar and dissimilar users under the framework of collaborative filtering. Extensive analyses on three datasets, namely MovieLens, Netflix and Amazon, show that our method performs much better than the standard collaborative filtering algorithm for both accuracy and diversity.
EFFECTS OF INDIVIDUAL'S SELF-EXAMINATION ON COOPERATION IN PRISONER'S DILEMMA GAME
Authors: GUAN JIAN-YUE , SUN JIN-TU , WANG YING-HAI
Published: October 2010

We study a spatial evolutionary prisoner's dilemma game on regular network's one-dimensional regular ring and two-dimensional square lattice. The individuals located on the sites of networks can either cooperate with their neighbors or defect. The effects of individual's self-examination are introduced. Using Monte Carlo simulations and pair approximation method, we investigate the average density of cooperators in the stationary state for various values of payoff parameters b and the time interval Δt. The effects of the fraction p of players in the system who are using the self-examination on cooperation are also discussed. It is shown that compared with the case of no individual's self-examination, the persistence of cooperation is inhibited when the payoff parameter b is small and at certain Δt (Δt > 0) or p (p > 0), cooperation is mostly inhibited, while when b is large, the emergence of cooperation can be remarkably enhanced and mostly enhanced at Δt = 0 or p = 1.
THE OPTIMUM OF SYNCHRONIZABILITY IN COMPLEX NETWORKS
Authors: MA PEI-JIE , WANG BING-HONG
Published: October 2010

In this brief report, we investigate the synchronizability of the complex network. In order to optimize the synchronizability, we propose a method by introducing a weight matrix, which makes the synchronized states stable for the widest range of the overall coupling strength. We give a proof in mathematics and gain the exact form of the weight matrix, which is equal to Lβ. Matrix L is the one that describes the optimal network and matrix β is constructed by the eigenvalues and eigenvectors of the usual Laplacian matrix. This result may provide us insight into the synchronization of complex network more deeply.
PROPAGATION CHARACTERISTICS OF THE DIVERGENCE OF ELEMENTARY CELLULAR AUTOMATA
Authors: DEL REY A. MARTIN , DIOS A. QUEIRUGA , SÁNCHEZ G. RODRÍGUEZ
Published: October 2010

In this work the notion of divergence of elementary cellular automata is introduced and it is analyzed from a cryptographic point of view. Specifically, the balancedness and propagation characteristics are analyzed.
EVOLUTION OF COORDINATION IN SOCIAL NETWORKS: A NUMERICAL STUDY
Authors: TOMASSINI MARCO , PESTELACCI ENEA
Published: October 2010

Coordination games are important to explain efficient and desirable social behavior. Here we study these games by extensive numerical simulation on networked social structures using an evolutionary approach. We show that local network effects may promote selection of efficient equilibria in both pure and general coordination games and may explain social polarization. These results are put into perspective with respect to known theoretical results. The main insight we obtain is that clustering, and especially community structure in social networks has a positive role in promoting socially efficient outcomes.
STARTING HOMOCLINIC TANGENCIES NEAR 1 : 1 RESONANCES
Authors: PÁEZ CHÁVEZ JOSEPH
Published: October 2010

We construct a theory-based numerical method for starting the continuation of homoclinic tangencies near 1 : 1 resonances, for systems with arbitrary dimension ≥ 2. The core of the method is numerical center manifold reduction and flow approximation. The reduction is implemented by means of the homological equation. The starting procedure is applied in numerical examples.
COEXISTENCE OF MULTIFARIOUS EXACT NONLINEAR WAVE SOLUTIONS FOR GENERALIZED b-EQUATION
Authors: LIU RUI
Published: October 2010

In this paper, we consider the generalized b-equation ut - uxxt + (b + 1)u2ux = buxuxx + uxxx. For a given constant wave speed, we investigate the coexistence of multifarious exact nonlinear wave solutions including smooth solitary wave solution, peakon wave solution, smooth periodic wave solution, single singular wave solution and periodic singular wave solution. Not only is the coexistence shown, but the concrete expressions are given via phase analysis and special integrals. From our work, it can be seen that the types of exact nonlinear wave solutions of the generalized b-equation are more than that of the b-equation. Many previous results are turned to our special cases. Also, some conjectures and questions are presented.
AUTOASSOCIATIVE MEMORY CELLULAR NEURAL NETWORKS
Authors: ITOH MAKOTO , CHUA LEON O.
Published: October 2010

An autoassociative memory is a device which accepts an input pattern and generates an output as the stored pattern which is most closely associated with the input. In this paper, we propose an autoassociative memory cellular neural network, which consists of one-dimensional cells with spatial derivative inputs, thresholds and memories. Computer simulations show that it exhibits good performance in face recognition: The network can retrieve the whole from a part of a face image, and can reproduce a clear version of a face image from a noisy one. For human memory, research on "visual illusions" and on "brain damaged visual perception", such as the Thatcher illusion, the hemispatial neglect syndrome, the split-brain, and the hemispheric differences in recognition of faces, has fundamental importance. We simulate them in this paper using an autoassociative memory cellular neural network. Furthermore, we generate many composite face images with spurious patterns by applying genetic algorithms to this network. We also simulate a morphing between two faces using autoassociative memory.
MULTISCROLL CHAOTIC ATTRACTORS FROM A HYSTERESIS BASED TIME-DELAY DIFFERENTIAL EQUATION
Authors: KILINÇ SELÇUK , YALÇIN MÜŞTAK E. , ÖZOGUZ SERDAR
Published: October 2010

In this paper, the generation of multiscroll chaotic attractors derived from a time-delay differential equation is presented. The proposed system is represented by only one first-order differential equation including time-delayed state variable, and employs hysteresis function as the nonlinear characteristic. The generalization of the introduced system is based on adding multihysteresis nonlinear characteristic which leads to n-scroll chaotic attractors. The circuit implementation of the proposed system and some experimental results referring to two-, three-, four-, and five-scroll chaotic attractors are reported.
HYPERCHAOS IN A NEW FOUR-DIMENSIONAL AUTONOMOUS SYSTEM
Authors: CORREIA MARCOS J. , RECH PAULO C.
Published: October 2010

In this letter we report a new four-dimensional autonomous system, constructed from a chaotic Lorenz system by introducing an adequate feedback controller to the third equation. We show that when parameters are conveniently chosen, the control method can drive the chaotic Lorenz system to hyperchaotic regions. Analytical and numerical procedures are conducted to study the dynamical behaviors of the proposed new system.
FROM KINETIC ART TO IMMATERIAL ART THROUGH CHAOTIC SYNCHRONIZATION
Authors: BELLUOMO PAOLA , CAMERANO CRISTOFORO , FORTUNA LUIGI , FRASCA MATTIA
Published: October 2010

In this paper, the idea of using simple robots and nonlinear dynamics based devices is strengthened in order to create an interactive platform to generate artistic patterns incorporating the concept of relating kinematic art with immaterial art paradigm.
THEORETICAL MODEL FOR THE CALCULATION OF OPTICAL PROPERTIES OF GOLD NANOPARTICLES
Authors: MENDOZA-GARCÍA A. , ROMERO-DEPABLOS A. , ORTEGA M. A. , PAZ J. L. , ECHEVARRÍA L.
Published: October 2010

We have developed an analytical method to describe the optical properties of nanoparticles, whose results are in agreement with the observed experimental behavior according to the size of the nanoparticle under analysis. Our considerations to describe plasmonic absorption and dispersion are based on the combination of the two-level molecular system and the two-dimensional quantum box models. Employing the optical stochastic Bloch equations, we have determined the system's coherence, from which we have calculated expressions for the absorption coefficient and refractive index. The innovation of this methodology is that it allows us to take into account the solvent environment, which induce quantum effects not considered by classical treatments.
HELMHOLTZ SOLITONS IN OPTICAL MATERIALS WITH A DUAL POWER-LAW REFRACTIVE INDEX
Authors: CHRISTIAN J. M. , McDONALD G. S. , CHAMORRO-POSADA P.
Published: October 2010

A nonlinear Helmholtz equation is proposed for modelling scalar optical beams in uniform planar waveguides whose refractive index exhibits a purely-focusing dual power-law dependence on the electric field amplitude. Two families of exact analytical solitons, describing forward- and backward-propagating beams, are derived. These solutions are physically and mathematically distinct from those recently discovered for related nonlinearities. The geometry of the new solitons is examined, conservation laws are reported, and classic paraxial predictions are recovered in a simultaneous multiple limit. Conventional semi-analytical techniques assist in studying the stability of these nonparaxial solitons, whose propagation properties are investigated through extensive simulations.