bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the Luminex xTAG Respiratory Viral Panel with xTAG Respiratory Viral Panel Fast for Diagnosis of Respiratory Virus Infections
Authors: Pabbaraju Kanti , Wong Sallene , Tokaryk Kara L. , Fonseca Kevin , Drews Steven J. 
Published: March 2011

ABSTRACT
Nucleic acid tests are sensitive and specific and provide a rapid diagnosis, making them invaluable for patient and outbreak management. Multiplex PCR assays have additional advantages in providing an economical and comprehensive panel for many common respiratory viruses. Previous reports have shown the utility of the xTAG respiratory viral panel (RVP) assay manufactured by Luminex Molecular Diagnostics for this purpose. A newer generation of this kit, released in Canada in early 2010, is designed to simplify the procedure and reduce the turnaround time by about 24 h. The assay methodology and targets included in this version of the kit are different; consequently, the objective of this study was to compare the detection of a panel of respiratory viral targets using the older Luminex xTAG RVP (RVP Classic) assay with that using the newer xTAG RVP Fast assay. This study included 334 respiratory specimens that had been characterized for a variety of respiratory viral targets; all samples were tested by both versions of the RVP assay in parallel. Overall, the RVP Classic assay was more sensitive than the RVP Fast assay (88.6% and 77.5% sensitivities, respectively) for all the viral targets combined. Targets not detected by the RVP Fast assay included primarily influenza B virus, parainfluenza virus type 2, and human coronavirus 229E. A small number of samples positive for influenza A virus, respiratory syncytial virus B, human metapneumovirus, and parainfluenza virus type 1 were not detected by the RVP Classic assay and in general had low viral loads.
Modified Multiple-Locus Variable-Number Tandem-Repeat Analysis for Rapid Identification and Typing of Clostridium difficile during Institutional Outbreaks
Authors: Broukhanski George , Low Donald E. , Pillai Dylan R. 
Published: March 2011

ABSTRACT

A modified multiple-locus variable-number tandem-repeat analysis (MMLVA) method was validated on
Clostridium difficile
-infected stool specimens from institutional outbreaks. The method allows simultaneous detection of toxin genes, deletions, and tandem repeats from cultured isolates or stool specimens. Results were used to aid institutional outbreak investigation by identifying clusters of NAP1/027.
Myocarditis Caused by Human Parainfluenza Virus in an Immunocompetent Child Initially Associated with 2009 Influenza A (H1N1) Virus
Authors: Romero-Gómez María P. , Guereta Luis , Pareja-Grande Julia , Martínez-Alarcón José , Casas Inmaculada , Ruiz-Carrascoso Guillermo , de Ory Fernando , Pozo Francisco 
Published: March 2011

ABSTRACT
The association between respiratory viruses and myocarditis has hardly ever been described. We report a case of acute myocarditis in an immunocompetent child associated with the presence of parainfluenza virus type 3 infection, in a context of recent influenza illness, confirmed by molecular and serological studies.
Human Immunodeficiency Virus Type 1 Infection Is Associated with Increased NK Cell Polyfunctionality and Higher Levels of KIR3DL1+NK Cells in Ugandans Carrying the HLA-B Bw4 Motif
Authors: Eller Michael A. , Koehler Rebecca N. , Kijak Gustavo H. , Eller Leigh Anne , Guwatudde David , Marovich Mary A. , Michael Nelson L. , de Souza Mark S. , Wabwire-Mangen Fred , Robb Merlin L. , Currier Jeffrey R. , Sandberg Johan K. 
Published: March 2011

ABSTRACTNatural killer (NK) cells are important innate effector cells controlled by an array of activating and inhibitory receptors. Some alleles of the inhibitory killer-cell immunoglobulin-like receptor KIR3DL1 in combination with its HLA class I ligand Bw4 have been genetically associated with slower HIV-1 disease progression. Here, we observed that the presence of HLA-B Bw4 was associated with elevated frequencies of KIR3DL1+CD56dimNK cells in chronically HIV-1-infected individuals from the rural district of Kayunga, Uganda. In contrast, levels of KIR2DL1+CD56dimNK cells were decreased, and levels of KIR2DL3+CD56dimNK cells were unchanged in infected subjects carrying their respective HLA-C ligands. Furthermore, the size of the KIR3DL1+NK cell subset correlated directly with viral load, and this effect occurred only in HLA-B Bw4+patients, suggesting that these cells expand in response to viral replication but may have relatively poor antiviral capacity. In contrast, no association with viral load was present for KIR2DL1+and KIR2DL3+NK cells. Interestingly, chronic HIV-1 infection was associated with an increased polyfunctional response in the NK cell compartment, and, upon further investigation, KIR3DL1+CD56dimNK cells exhibited a significantly increased functional response in the patients carrying HLA-B Bw4. These results indicate that chronic HIV-1 infection is associated with increased NK cell polyfunctionality and elevated levels of KIR3DL1+NK cells in Ugandans carrying the HLA-B Bw4 motif.
Immune Evasion of Porcine Reproductive and Respiratory Syndrome Virus through Glycan Shielding Involves both Glycoprotein 5 as Well as Glycoprotein 3
Authors: Vu Hiep L. X. , Kwon Byungjoon , Yoon Kyoung-Jin , Laegreid William W. , Pattnaik Asit K. , Osorio Fernando A. 
Published: March 2011

ABSTRACT

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response
in vivo
. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, in two of its envelope glycoproteins, one in GP3 (position 131) and the other in GP5 (position 51). To determine the influence of these missing N-glycosylation sites on the distinct neutralization phenotype of PRRSV-01, a chimeric virus (FL01) was generated by replacing the structural genes of type II PRRSV strain FL12 cDNA infectious clone with those from PRRSV-01. N-glycosylation sites were reintroduced into GP3 and GP5 of FL01, separately or in combination, by site-directed mutagenesis. Reintroduction of the N-glycosylation site in either GP3 or GP5 allowed recovery of
in vivo
and
in vitro
glycan shielding capacity, with an additive effect when these sites were reintroduced into both glycoproteins simultaneously. Although the loss of these glycosylation sites has seemingly occurred naturally (presumably by passage through cell cultures), PRRSV-01 virus quickly regains these glycosylation sites through replication
in vivo
, suggesting that a strong selective pressure is exerted at these sites. Collectively, our data demonstrate the involvement of an N-glycan moiety located in GP3 in glycan shield interference.
Identification of a Novel Apoptosis Suppressor Gene from the Baculovirus Lymantria dispar Multicapsid Nucleopolyhedrovirus
Authors: Yamada Hayato , Shibuya Miyuki , Kobayashi Michihiro , Ikeda Motoko 
Published: March 2011

ABSTRACT

Ld652Y cells from
Lymantria dispar
readily undergo apoptosis upon infection with a variety of nucleopolyhedroviruses (NPVs), while
L. dispar
multicapsid NPV (LdMNPV) infection of Ld652Y cells results in the production of a high titer of progeny viruses. Here, we identify a novel LdMNPV apoptosis suppressor gene,
apsup
, which functions to suppress apoptosis induced in Ld652Y cells by infection with vAcΔp35, a
p35
-defective recombinant
Autographa californica
MNPV.
apsup
also suppresses apoptosis of Ld652Y cells induced by actinomycin D and UV exposure. Apsup is expressed in LdMNPV-infected Ld652Y cells late in infection, and RNA interference-mediated
apsup
ablation induces apoptosis of LdMNPV-infected Ld652Y cells.
The Mouse Cytomegalovirus Glycoprotein m155 Inhibits CD40 Expression and Restricts CD4 T Cell Responses
Authors: Loewendorf Andrea I. , Steinbrueck Lars , Peter Christoph , Busche Andreas , Benedict Chris A. , Kay-Jackson Penelope C. 
Published: March 2011

ABSTRACTCytomegaloviruses (CMV) utilize a variety of immunomodulatory strategies to facilitate the establishment of lifelong persistence in their infected hosts. We show that the mouse CMV (MCMV) m155 open reading frame (ORF) is required for the posttranscriptional inhibition of CD40 expression in infected antigen-presenting cells. Consistent with the known importance of CD40-mediated costimulation of T cells, a m155-deficient virus induces enhanced MCMV epitope-specific CD4 T cell responses.
Activities of ICP0 Involved in the Reversal of Silencing of Quiescent Herpes Simplex Virus 1
Authors: Ferenczy Michael W. , Ranayhossaini Daniel J. , DeLuca Neal A. 
Published: March 2011

ABSTRACT
ICP0 is a transcriptional activating protein required for the efficient replication and reactivation of latent herpes simplex virus 1 (HSV-1). Multiple regions of ICP0 contribute its activity, the most prominent of which appears to be the RING finger, which confers E3 ubiquitin ligase activity. A region in the C terminus of ICP0 has also been implicated in several activities, including the disruption of a cellular repressor complex, REST/CoREST/HDAC1/2/LSD1. We used quiescent infection of MRC-5 cells with a virus that does not express immediate-early proteins, followed by superinfection with various viral mutants to quantify the ability of ICP0 variants to reactivate gene expression and alter chromatin structure. Superinfection with wild-type virus resulted in a 400-fold increase in expression from the previously quiescent d109 genome, the removal of heterochromatin and histones from the viral genome, and an increase in histone marks associated with activated transcription. RING finger mutants were unable to reactivate transcription or remove heterochromatin from d109, while mutants that are unable to bind CoREST activate gene expression from quiescent d109, albeit to a lesser degree than the wild-type virus. One such mutant, R8507, resulted in the partial removal of heterochromatin. Infection with R8507 did not result in the hyperacetylation of H3 and H4. The results demonstrate that (i) consistent with previous findings, the RING finger domain of ICP0 is required for the activation of quiescent genomes, (ii) the RF domain is also crucial for the ultimate removal of repressive chromatin, (iii) activities or interactions specified by the carboxy-terminal region of ICP0 significantly contribute to activation, and (iv) while the effects of the R8507 on chromatin are consistent with a role for REST/CoREST/HDAC1/2/LSD1 in the repression of quiescent genomes, the mutation may also affect other activities involved in derepression.
A Virus-Binding Hot Spot on Human Angiotensin-Converting Enzyme 2 Is Critical for Binding of Two Different Coronaviruses
Authors: Wu Kailang , Chen Lang , Peng Guiqing , Zhou Wenbo , Pennell Christopher A. , Mansky Louis M. , Geraghty Robert J. , Li Fang 
Published: March 2011

ABSTRACT
How viruses evolve to select their receptor proteins for host cell entry is puzzling. We recently determined the crystal structures of NL63 coronavirus (NL63-CoV) and SARS coronavirus (SARS-CoV) receptor-binding domains (RBDs), each complexed with their common receptor, human angiotensin-converting enzyme 2 (hACE2), and proposed the existence of a virus-binding hot spot on hACE2. Here we investigated the function of this hypothetical hot spot using structure-guided biochemical and functional assays. The hot spot consists of a salt bridge surrounded by hydrophobic tunnel walls. Mutations that disturb the hot spot structure have significant effects on virus/receptor interactions, revealing critical energy contributions from the hot spot structure. The tunnel structure at the NL63-CoV/hACE2 interface is more compact than that at the SARS-CoV/hACE2 interface, and hence RBD/hACE2 binding affinities are decreased either by NL63-CoV mutations decreasing the tunnel space or by SARS-CoV mutations increasing the tunnel space. Furthermore, NL63-CoV RBD inhibits hACE2-dependent transduction by SARS-CoV spike protein, a successful application of the hot spot theory that has the potential to become a new antiviral strategy against SARS-CoV infections. These results suggest that the structural features of the hot spot on hACE2 were among the driving forces for the convergent evolution of NL63-CoV and SARS-CoV.
A Role for the Small GTPase Rab6 in Assembly of Human Cytomegalovirus
Authors: Indran Sabarish V. , Britt William J. 
Published: March 2011

ABSTRACT
In human-cytomegalovirus (HCMV)-infected cells, the localization of the viral protein pp150 to the virus assembly compartment (AC) is dependent on its direct interaction with the cellular protein Bicaudal D1 through a dynein- and microtubule-dependent mechanism. We found that the small GTPase Rab6 also interacts indirectly with pp150 through its interaction with Bicaudal D1. Inhibition of Rab6 activity in HCMV-infected cells interrupted the intracellular trafficking of pp150, significantly reducing infectious virus production without affecting the formation of the AC, arguing for an important function for this cellular GTPase in the intracellular localization of pp150 during virus assembly.
Transgenic Expression of Polyomavirus Middle T Antigen in the Mouse Prostate Gives Rise to Carcinoma
Authors: Lee Sang Hyun , Jia Shidong , Zhu Yanni , Utermark Tamara , Signoretti Sabina , Loda Massimo , Schaffhausen Brian , Roberts Thomas M. 
Published: March 2011

ABSTRACTThe middle T (MT) antigen of polyomavirus has provided fundamental insights into the regulation of mammalian cell growthin vitroand important animal models for the analysis of tumor induction. The mouse mammary tumor virus (MMTV)-MT model of breast cancer has been important for probing the cellular signaling pathways in mammary tumorigenesis. MT itself has no intrinsic enzymatic activity but, rather, transforms by binding to and activating key intracellular signaling molecules, phosphatidylinositol 3-kinase (PI3-kinase) being the best studied of these. Thus, MT mimics a constitutively activated receptor tyrosine kinase (RTK). Our recent work suggests that MT signaling, like that of RTKs, is often quite dependent on cellular contextin vitro. Here, we examine contextual effects on signaling in animal models as well. In this study, we generated transgenic mice in which MT is expressed in the mouse prostate under the control of an (ARR)2-Probasin promoter. All male transgenic mice displayed mouse prostatic intraepithelial neoplasia (mPIN) in the ventral and dorsal/lateral prostate as early as 8 weeks of age. Notably, during the course of tumor development over time, invasive cancer, reactive stroma, and infiltration of inflammatory cells were seen. Transcriptional profiling analyses show regulation of multiple pathways, with marked upregulation of both the NF-κB and inflammatory pathways. Comparison of expression profiles of our MT prostate model with those from an MMTV-MT breast model (23) shows both tissue-specific and tissue-independent MT effects. The signature of genes regulated by MT in a tissue-independent manner may have prognostic value.
A Novel Prodrug of Epigallocatechin-3-gallate: Differential Epigenetic hTERT Repression in Human Breast Cancer Cells
Authors: Meeran Syed M. , Patel Shweta N. , Chan Tak-Hang , Tollefsbol Trygve O. 
Published: March 2011

Abstract
Epigallocatechin-3-gallate (EGCG), a major component of green tea polyphenols (GTP), has been reported to downregulate telomerase activity in breast cancer cells thereby increasing cellular apoptosis and inhibiting cellular proliferation. However, the major concerns with GTPs are their bioavailability and stability under physiologic conditions. In the present study, we show that treatments with EGCG and a novel prodrug of EGCG (pro-EGCG or pEGCG) dose- and time-dependently inhibited the proliferation of human breast cancer MCF-7 and MDA-MB-231 cells but not normal control MCF10A cells. Furthermore, both EGCG and pro-EGCG inhibited the transcription of hTERT (human telomerase reverse transcriptase), the catalytic subunit of telomerase, through epigenetic mechanisms in estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cells. The downregulation of hTERT expression was found to be because of hTERT promoter hypomethylation and histone deacetylations, mediated at least partially through inhibition of DNA methyltransferase and histone acetyltransferase activities, respectively. In addition, we also observed that EGCG and pEGCG can remodel chromatin structures of the hTERT promoter by decreasing the level of acetyl-H3, acetyl-H3K9, and acetyl-H4 to the hTERT promoter. EGCG and pEGCG induced chromatin alterations that facilitated the binding of many hTERT repressors such as MAD1 and E2F-1 to the hTERT regulatory region. Depletion of E2F-1 and MAD1 by using siRNA reversed the pEGCG downregulated hTERT expression and associated cellular apoptosis differently in ER-positive and ER-negative breast cancer cells. Collectively, our data provide new insights into breast cancer prevention through epigenetic modulation of telomerase by using pro-EGCG, a more stable form of EGCG, as a novel chemopreventive compound. Cancer Prev Res; 4(8); 1243–54. ©2011 AACR.
Clinical Characteristics of Pulmonary Hypertension in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Thenappan Thenappan , Shah Sanjiv J. , Gomberg-Maitland Mardi , Collander Brett , Vallakati Ajay , Shroff Pranavkumar , Rich Stuart 
Published: March 2011

Background—
Pulmonary vascular disease associated with left-side heart failure and preserved ejection fraction (PH-HFpEF) is an increasingly common cause of pulmonary hypertension. The distinction between PH-HFpEF and pulmonary arterial hypertension (PAH) is important because therapies indicated for PAH can be detrimental in HFpEF. The characteristic features of PH-HFpEF are understudied.

Methods and Results—

In a cross-sectional study, we compared the clinical, echocardiographic, and hemodynamic features of PH-HFpEF (n=100), with PAH (n=522), and HFpEF without pulmonary vascular disease (n=45). We determined the clinical characteristics that best differentiated PH-HFpEF from PAH. Compared with patients with PAH, patients with PH-HFpEF were older; had a higher prevalence of cardiovascular comorbidities; had worse exercise capacity and renal function; more frequently had left atrial enlargement; and less frequently had right atrial enlargement. PH was less severe in PH-HFpEF patients than in PAH patients (pulmonary vascular resistance 4.8 [interquartile range 3 to 8.4] versus 10.9 [interquartile range 7.4 to 15.7] Wood units;
P
<0.001). Old age, the presence of hypertension and coronary artery disease, the absence of right atrial enlargement, higher aortic systolic pressure, higher mean right atrial pressure, and higher cardiac output best differentiated PH-HFpEF from PAH (area under the receiver operating characteristics curve; curve 0.97). Compared with HFpEF patients without pulmonary hypertension, PH-HFpEF patients were often female and more symptomatic, more often had right ventricular hypertrophy and right atrial enlargement, and had higher right atrial pressure.

Conclusions—
These data should help better identify PH-HFpEF, an entity that has become increasingly recognized and difficult to treat.
Neuromodulation by soy diets or equol: Anti-depressive & anti-obesity-like influences, age- & hormone-dependent effects
Authors: Blake Crystal , Fabick Kimberly M , Setchell Kenneth DR , Lund Trent D , Lephart Edwin D 
Published: March 2011

Abstract

Background
Soy-derived isoflavones potentially protect against obesity and depression. In five different studies we examined the influence of soy-containing diets or equol injections on depression, serotonin levels, body weight gain (BW) and white adipose tissue (WAT) deposition in female Long-Evans rats at various stages of life [rats were intact, ovariectomized or experienced natural ovarian failure (NOF)].

Results
In general, animals fed a soy-rich diet (Phyto-600) and/or administered equol (@ 5 mg/kg/day) displayed significant decreases in BW and WAT compared to a low-soy diet. When equol was injected alone (5 mg/kg/day), experiments 1, 4, and 5 demonstrated that body weight was significantly decreased. Equol has body weight control effects in females that are dependent on ovarian status and/or age of diet initiation. Experiments 1-4 all displayed no significant differences in depressive-related behavior as measured by the Prosolt forced swim test (PFST) when soy-rich (Phyto-600) or low-soy diets (Phyto-low) or equol treatments (5 mg/kg/day) were tested in female rats at various ages or hormonal status. Results of all the experiments are not presented here due to space limitations, but data from experiment 5 are presented. From conception female rats were exposed to either: a) a soy-rich (Phyto-600) or b) low-soy diet (Phyto-low). After 290 days all rats experienced NOF. At 330 days-old the animals were examined in the Porsolt forced swim test (PFST). One month later a second PFST was performed [after Phyto-low fed animals were injected with equol (5 mg/kg/day) for one week prior to the second PFST]. At the first PFST, serotonin and mobility levels were significantly decreased in the Phyto-low fed animals compared to animals that consumed the Phyto-600 diet. After equol injections at the second PFST, mobility and serotonin levels significantly increased in aged NOF rats fed the Phyto-low diet (to levels comparable to Phyto-600 fed animals).

Conclusions
Consumption of dietary isoflavones or equol exposure in rats has body weight controlling effects and equol specifically may have antidepressant potential dependent upon diet initiation and/or dosage of treatments. The current study demonstrates that equol is able to decrease body weight, abdominal WAT, and depressive-related behavior. While other factors and mechanisms may play a role, in part, the present results provide a greater understanding of how isoflavonoid molecules modulate the brain's influence on behavior.