bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved Detection of Nasopharyngeal Cocolonization by Multiple Pneumococcal Serotypes by Use of Latex Agglutination or Molecular Serotyping by Microarray
Authors: Turner Paul , Hinds Jason , Turner Claudia , Jankhot Auscharee , Gould Katherine , Bentley Stephen D. , Nosten François , Goldblatt David 
Published: March 2011

ABSTRACT

Identification of
Streptococcus pneumoniae
in the nasopharynx is critical for an understanding of transmission, estimates of vaccine efficacy, and possible replacement disease. Conventional nasopharyngeal swab (NPS) culture and serotyping (the WHO protocol) is likely to underestimate multiple-serotype carriage. We compared the WHO protocol with methods aimed at improving cocolonization detection. One hundred twenty-five NPSs from an infant pneumococcal-carriage study, containing ≥1 serotype by WHO culture, were recultured in duplicate. A sweep of colonies from one plate culture was serotyped by latex agglutination. DNA extracted from the second plate was analyzed by
S. pneumoniae
molecular-serotyping microarray. Multiple serotypes were detected in 11.2% of the swabs by WHO culture, 43.2% by sweep serotyping, and 48.8% by microarray. Sweep and microarray were more likely to detect multiple serotypes than WHO culture (
P
< 0.0001). Cocolonization detection rates were similar between microarray and sweep, but the microarray identified the greatest number of serotypes. A common serogroup type was identified in 95.2% of swabs by all methods. WHO methodology significantly underestimates multiple-serotype carriage compared to these alternate methods. Sweep serotyping is cost-effective and field deployable but may fail to detect serotypes at low abundance, whereas microarray serotyping is more costly and technology dependent but may detect these additional minor carried serotypes.
Aptima Combo 2 Testing Detected Additional Cases of Neisseria gonorrhoeae Infection in Men and Women in Community Settings
Authors: Kapala Julius , Biers Kathy , Cox Michael , Kamionka Margaret , Sumner Jeff , Toor Ramandeep , Gilchrist Jodi , Jang Dan , Smieja Marek , Chernesky Max 
Published: March 2011

ABSTRACT

Aptima Combo 2 (AC2)
Neisseria gonorrhoeae
testing of 81,405 patients who were tested by culture and 14,666 who were AC2 tested for
Chlamydia trachomatis
detected 142 extra infections and confirmed 106 culture-positive samples (the positivity rate increased from 0.13 in testing by culture to 0.26 in testing by AC2). Retrievable AC2 positive samples were confirmed (98.5%) by an alternate AGC test.
Comparison of the Xpert MTB/RIF Test with an IS
6110
-TaqMan Real-Time PCR Assay for Direct Detection of Mycobacterium tuberculosis in Respiratory and Nonrespiratory Specimens
Authors: Armand Sylvie , Vanhuls Pascale , Delcroix Guy , Courcol René , Lemaître Nadine 
Published: March 2011

ABSTRACT

The sensitivities of the Xpert MTB/RIF test and an in-house IS
6110
-based real-time PCR using TaqMan probes (IS
6110
-TaqMan assay) for the detection of
Mycobacterium tuberculosis
complex (MTBC) DNA were compared by use of 117 clinical specimens (97 culture positive and 20 culture negative for MTBC) that were frozen in sediment. The 97 clinical specimens included 60 respiratory and 37 nonrespiratory specimens distributed into 36 smear-positive and 61 smear-negative specimens. Among the 97 culture-positive specimens, 4 had rifampin-resistant isolates. Both methods were highly specific and exhibited excellent sensitivity (100%) with smear-positive specimens. The sensitivity of the Xpert MTB/RIF test with the whole smear-negative specimens was more reduced than that of the IS
6110
-TaqMan assay (48
versus
69%,
P
= 0.005). Both methods exhibited similar sensitivities with smear-negative respiratory specimens, but the Xpert MTB/RIF test had lower sensitivity with smear-negative nonrespiratory specimens than the IS
6110
-TaqMan assay (37 versus 71%,
P
= 0.013). Finally, the sensitivities of the Xpert MTB/RIF test and the IS
6110
-TaqMan assay were 79% and 84%, respectively, with respiratory specimens and 53% and 78%, respectively (
P
= 0.013), with nonrespiratory specimens. The Xpert MTB/RIF test correctly detected the rifampin resistance in smear-positive specimens but not in the one smear-negative specimen. The Xpert MTB/RIF test is a simple rapid method well adapted to a routine laboratory that appeared to be as sensitive as the IS
6110
-TaqMan assay with respiratory specimens but less sensitive with paucibacillary specimens, such as smear-negative nonrespiratory specimens.
Herpes Simplex Virus Glycoproteins gB and gD Function in a Redundant Fashion To Promote Secondary Envelopment
Authors: Johnson David C. , Wisner Todd W. , Wright Catherine C. 
Published: March 2011

ABSTRACT

Egress of herpes simplex virus (HSV) and other herpesviruses from cells involves extensive modification of cellular membranes and sequential envelopment and deenvelopment steps. HSV glycoproteins are important in these processes, and frequently two or more glycoproteins can largely suffice in any step. Capsids in the nucleus undergo primary envelopment at the inner nuclear membrane (INM), and then enveloped virus particles undergo deenvelopment by fusing with the outer nuclear membrane (ONM). Capsids delivered into the cytoplasm then undergo secondary envelopment, involving
trans
-Golgi network (TGN) membranes. The deenvelopment step involves HSV glycoproteins gB and gH/gL acting in a redundant fashion. This fusion has features common to the fusion that occurs between the virion envelope and cellular membranes when HSV enters cells, a process requiring gB, gD, and gH/gL. Whether HSV gD also participates (in a redundant fashion with gB or gH/gL) in deenvelopment has not been characterized. Secondary envelopment in the cytoplasm is known to involve HSV gD and gE/gI, also acting in a redundant fashion. Whether gB might also contribute to secondary envelopment, collaborating with gD and gE/gI, is also not clear. To address these questions, we constructed an HSV double mutant lacking gB and gD. The HSV gB
−
/gD
−
mutant exhibited no substantial defects in nuclear egress. In contrast, secondary envelopment was markedly reduced, and there were numerous unenveloped capsids that accumulated in the cytoplasm, as well as increased numbers of partially enveloped capsids and morphologically aberrant enveloped particles with thicker, oblong tegument layers. These defects were different from those observed with HSV gD
−
/gE
−
/gI
−
mutants, which accumulated capsids in large, aggregated masses in the cytoplasm. Our results suggest that HSV gB functions in secondary envelopment, apparently acting downstream of gE/gI.
Two Closely Related Env Antigens from the Same Patient Elicited Different Spectra of Neutralizing Antibodies against Heterologous HIV-1 Isolates
Authors: Vaine Michael , Duenas-Decamp Maria , Peters Paul , Liu Qin , Arthos James , Wang Shixia , Clapham Paul , Lu Shan 
Published: March 2011

ABSTRACT
Identification of immunogens capable of eliciting broadly neutralizing antibody (NAb) responses against HIV-1 is a major goal toward the development of an AIDS vaccine. Despite significant progress in understanding the structural features of the HIV-1 envelope glycoprotein (Env) and the discovery of multiple broadly neutralizing monoclonal antibodies with defined antigenic structures, the design of optimal Env immunogens to elicit broad NAbs remains a major challenge. As the structural determinants of Env immunogenicity remain unclear, we assessed two closely related Env antigens isolated from the same HIV-1-infected patient with different phenotypic features to identify what may result in a favorable immunogenic profile. One Env, B33, isolated from brain, was highly macrophage tropic with a high CD4 affinity, while the other, LN40, isolated from the lymph nodes, was poorly macrophage tropic with a low CD4 affinity. Using a DNA prime-protein boost approach, rabbits primed with LN40 Env antigen had a NAb response against heterologous primary isolates, while B33 Env antigens were capable of eliciting NAbs against only homologous and sensitive viral isolates. Further analysis revealed that the specificity of NAbs elicited by the LN40 antigen mapped to limited residues within or flanking the CD4 binding site. Certain key structural determinants were identified that could differentiate primary Env immunogens based on their potential to elicit broader NAbs. This progress will facilitate the rational design of effective HIV-1 vaccine formulations with optimal Env antigens.
Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections
Authors: Johnson Philip L. F. , Kochin Beth F. , McAfee Megan S. , Stromnes Ingunn M. , Regoes Roland R. , Ahmed Rafi , Blattman Joseph N. , Antia Rustom 
Published: March 2011

ABSTRACTWhile T cell-based vaccines have the potential to provide protection against chronic virus infections, they also have the potential to generate immunopathology following subsequent virus infection. We develop a mathematical model to investigate the conditions under which T cells lead to protection versus adverse pathology. The model illustrates how the balance between virus clearance and immune exhaustion may be disrupted when vaccination generates intermediate numbers of specific CD8 T cells. Surprisingly, our model suggests that this adverse effect of vaccination is largely unaffected by the generation of mutant viruses that evade T cell recognition and cannot be avoided by simply increasing the quality (affinity) or diversity of the T cell response. These findings should be taken into account when developing vaccines against persistent infections.
The Polypyrimidine Tract-Binding Protein Affects Coronavirus RNA Accumulation Levels and Relocalizes Viral RNAs to Novel Cytoplasmic Domains Different from Replication-Transcription Sites
Authors: Sola Isabel , Galán Carmen , Mateos-Gómez Pedro A. , Palacio Lorena , Zúñiga Sonia , Cruz Jazmina L. , Almazán Fernando , Enjuanes Luis 
Published: March 2011

ABSTRACT
The coronavirus (CoV) discontinuous transcription mechanism is driven by long-distance RNA-RNA interactions between transcription-regulating sequences (TRSs) located at the 5′ terminal leader (TRS-L) and also preceding each mRNA-coding sequence (TRS-B). The contribution of host cell proteins to CoV transcription needs additional information. Polypyrimidine tract-binding protein (PTB) was reproducibly identified in association with positive-sense RNAs of transmissible gastroenteritis coronavirus (TGEV) TRS-L and TRS-B by affinity chromatography and mass spectrometry. A temporal regulation of PTB cytoplasmic levels was observed during infection, with a significant increase from 7 to 16 h postinfection being inversely associated with a decrease in viral replication and transcription. Silencing the expression of PTB with small interfering RNA in two cell lines (Huh7 and HEK 293T) led to a significant increase of up to 4-fold in mRNA levels and virus titer, indicating a negative effect of PTB on CoV RNA accumulation. During CoV infection, PTB relocalized from the nucleus to novel cytoplasmic structures different from replication-transcription sites in which stress granule markers T-cell intracellular antigen-1 (TIA-1) and TIA-1-related protein (TIAR) colocalized. PTB was detected in these modified stress granules in TGEV-infected swine testis cells but not in stress granules induced by oxidative stress. Furthermore, viral genomic and subgenomic RNAs were detected in association with PTB and TIAR. These cytoplasmic ribonucleoprotein complexes might be involved in posttranscriptional regulation of virus gene expression.
The Naturally Attenuated Kunjin Strain of West Nile Virus Shows Enhanced Sensitivity to the Host Type I Interferon Response
Authors: Daffis Stephane , Lazear Helen M. , Liu Wen Jun , Audsley Michelle , Engle Michael , Khromykh Alexander A. , Diamond Michael S. 
Published: March 2011

ABSTRACT

The host determinants that contribute to attenuation of the naturally occurring nonpathogenic strain of West Nile virus (WNV), the Kunjin strain (WNV
KUN
), remain unknown. Here, we show that compared to a highly pathogenic North American strain, WNV
KUN
exhibited an enhanced sensitivity to the antiviral effects of type I interferon. Our studies establish that the virulence of WNV
KUN
can be restored in cells and mice deficient in specific interferon regulatory factors (IRFs) or the common type I interferon receptor. Thus, WNV
KUN
is attenuated primarily through its enhanced restriction by type I interferon- and IRF-3-dependent mechanisms.
The Capsid-Binding Nucleolar Helicase DDX56 Is Important for Infectivity of West Nile Virus
Authors: Xu Zaikun , Anderson Robert , Hobman Tom C. 
Published: March 2011

ABSTRACT
Recent findings suggest that in addition to its role in packaging genomic RNA, the West Nile virus (WNV) capsid protein is an important pathogenic determinant, a scenario that requires interaction of this viral protein with host cell proteins. We performed an extensive multitissue yeast two-hybrid screen to identify capsid-binding proteins in human cells. Here we describe the interaction between WNV capsid and the nucleolar RNA helicase DDX56/NOH61. Coimmunoprecipitation confirmed that capsid protein binds to DDX56 in infected cells and that this interaction is not dependent upon intact RNA. Interestingly, WNV infection induced the relocalization of DDX56 from the nucleolus to a compartment in the cytoplasm that also contained capsid protein. This phenomenon was apparently specific for WNV, as DDX56 remained in the nucleoli of cells infected with rubella and dengue 2 viruses. Further analyses showed that DDX56 is not required for replication of WNV; however, virions secreted from DDX56-depleted cells contained less viral RNA and were 100 times less infectious. Together, these data suggest that DDX56 is required for assembly of infectious WNV particles.
The Influenza A Virus NS1 Protein Interacts with the Nucleoprotein of Viral Ribonucleoprotein Complexes
Authors: Robb Nicole C. , Chase Geoffrey , Bier Katja , Vreede Frank T. , Shaw Pang-Chui , Naffakh Nadia , Schwemmle Martin , Fodor Ervin 
Published: March 2011

ABSTRACT
The influenza A virus genome consists of eight RNA segments that associate with the viral polymerase proteins (PB1, PB2, and PA) and nucleoprotein (NP) to form ribonucleoprotein complexes (RNPs). The viral NS1 protein was previously shown to associate with these complexes, although it was not clear which RNP component mediated the interaction. Using individual TAP (tandem affinity purification)-tagged PB1, PB2, PA, and NP, we demonstrated that the NS1 protein interacts specifically with NP and not the polymerase subunits. The region of NS1 that binds NP was mapped to the RNA-binding domain.
Reverse Genetic Analysis of Ourmiaviruses Reveals the Nucleolar Localization of the Coat Protein in Nicotiana benthamiana and Unusual Requirements for Virion Formation
Authors: Crivelli Giulia , Ciuffo Marina , Genre Andrea , Masenga Vera , Turina Massimo 
Published: March 2011

ABSTRACT

Ourmia melon virus
(OuMV) is the type member of the genus
Ourmiavirus
. These viruses have a trisegmented genome, each part of which encodes a single protein. Ourmiaviruses share a distant similarity with other plant viruses only in their movement proteins (MP), whereas their RNA-dependent RNA polymerase (RdRP) shares features only with fungal viruses of the family
Narnaviridae
. Thus, ourmiaviruses are in a unique phylogenetic position among existing plant viruses. Here, we developed an agroinoculation system to launch infection in
Nicotiana benthamiana
plants. Using different combinations of the three segments, we demonstrated that RNA1 is necessary and sufficient for
cis
-acting replication in the agroinfiltrated area. RNA2 and RNA3, encoding the putative movement protein and the coat protein (CP), respectively, are both necessary for successful systemic infection of
N. benthamiana
. The CP is dispensable for long-distance transport of the virus through vascular tissues, but its absence prevents efficient systemic infection at the exit sites. Virion formation occurred only when the CP was translated from replication-derived RNA3. Transient expression of a green fluorescent protein-MP (GFP-MP) fusion via agroinfiltration showed that the MP is present in cytoplasmic connections across plant cell walls; in protoplasts the GFP-MP fusion stimulates the formation of tubular protrusions. Expression through agroinfiltration of a GFP-CP fusion displays most of the fluorescence inside the nucleus and within the nucleolus in particular. Nuclear localization of the CP was also confirmed through Western blot analysis of purified nuclei. The significance of several unusual properties of OuMV for replication, virion assembly, and movement is discussed in relation to other positive-strand RNA viruses.
THE EINSTEIN–BRILLOUIN–KELLER ACTION QUANTIZATION FOR DIRAC FERMIONS
Authors: ONORATO P. 
Published: March 2011

The Einstein–Brillouin–Keller semiclassical quantization and the topological Maslov index are used to compute the electronic structure of carbon based nanostructures with or without transverse magnetic field. The calculation is based on the Dirac Fermions approach in the limit of strong coupling for the pseudospin. The electronic bandstructure for carbon nanotubes and graphene nanoribbons are discussed, focusing on the role of the chirality and of the unbonded edges configuration respectively. The effects of a transverse uniform magnetic field are analyzed, the different kinds of classical trajectories are discussed and related to the corresponding energies. The development is concise, transparent, and involves only elementary integral calculus and provides a conceptual and intuitive introduction to the quantum nature of carbon nanostructures.
Targeting p53-Null Neuroblastomas through RLIP76
Authors: Singhal Jyotsana , Yadav Sushma , Nagaprashantha Lokesh Dalasanur , Vatsyayan Rit , Singhal Sharad S. , Awasthi Sanjay 
Published: March 2011

Abstract
The search for p53-independent mechanism of cancer cell killing is highly relevant to pediatric neuroblastomas, where successful therapy is limited by its transformation into p53-mutant and a highly drug-resistant neoplasm. Our studies on the drug-resistant p53-mutant as compared with drug-resistant p53 wild-type neuroblastoma revealed a novel mechanism for resistance to apoptosis: a direct role of p53 in regulating the cellular concentration of proapoptotic alkenals by functioning as a specific and saturable allosteric inhibitor of the alkenal–glutathione conjugate transporter, RLIP76. The RLIP76-p53 complex was showed by both immunoprecipitation analyses of purified proteins and immunofluorescence analysis. Drug transport studies revealed that p53 inhibited both basal and PKCα-stimulated transport of glutathione conjugates of 4HNE (GSHNE) and doxorubicin. Drug resistance was significantly greater for p53-mutant as compared with p53 wild-type neuroblastoma cell lines, but both were susceptible to depletion of RLIP76 by antisense alone. In addition, inhibition of RLIP76 significantly enhanced the cytotoxicity of cisplatin. Taken together, these studies provide powerful evidence for a novel mechanism for drug and apoptosis resistance in p53-mutant neuroblastoma, based on a model of regulation of p53-induced apoptosis by RLIP76, where p53 is a saturable and specific allosteric inhibitor of RLIP76, and p53 loss results in overexpression of RLIP76; thus, in the absence of p53, the drug and glutathione-conjugate transport activities of RLIP76 are enhanced. Most importantly, our findings strongly indicate RLIP76 as a novel target for therapy of drug-resistant and p53-mutant neuroblastoma. Cancer Prev Res; 4(6); 879–89. ©2011 AACR.
A Terrain-Following Coordinate with Smoothed Coordinate Surfaces
Authors: Klemp J. B. 
Published: March 2011

Abstract
An alternative form for a height-based terrain-following coordinate is presented here that progressively smoothes the coordinate surfaces with height to remove smaller scale (steeper) terrain structure from the surfaces. Testing this approach in comparison with traditional and hybrid terrain-following formulations in resting-atmosphere simulations demonstrates that it can significantly reduce artificial circulations caused by inaccuracies in the horizontal pressure gradient term. The simulations also suggest that some further improvement in the accuracy of the horizontal pressure gradient terms can be achieved using a simplified version of Mahrer’s approach, which can be implemented with little increase in computational cost or complexity.
The NSSL Hydrometeor Classification Algorithm in Winter Surface Precipitation: Evaluation and Future Development
Authors: Elmore Kimberly L. 
Published: March 2011

Abstract
The National Severe Storms Laboratory (NSSL) has developed a hydrometeor classification algorithm (HCA) for use with the polarimetric upgrade of the current Weather Surveillance Radar-1988 Doppler (WSR-88D) network. The algorithm was developed specifically for warm-season convection, but it will run regardless of season, and so its performance on surface precipitation type during winter events is examined here. The HCA output is compared with collocated (in time and space) observations of precipitation type provided by the public. The Peirce skill score (PSS) shows that the NSSL HCA applied to winter surface precipitation displays little skill, with a PSS of only 0.115. Further analysis indicates that HCA failures are strongly linked to the inability of HCA to accommodate refreezing below the first freezing level and to errors in the melting-level detection algorithm. Entrants in the 2009 American Meteorological Society second annual artificial intelligence competition developed classification methods that yield a PSS of 0.35 using a subset of available radar data merged with limited environmental data. Thus, when polarimetric radar data and environmental data are appropriately combined, more information about winter surface precipitation type is available than from either data source alone.
Assessment of Forecasts during Persistent Valley Cold Pools in the Bonneville Basin by the North American Mesoscale Model
Authors: Reeves Heather Dawn , Elmore Kimberly L. , Manikin Geoffrey S. , Stensrud David J. 
Published: March 2011

Abstract
North American Mesoscale Model (NAM) forecasts of low-level temperature and dewpoint during persistent valley cold pools in the Bonneville Basin of Utah are assessed. Stations near the east sidewall have a daytime cold and nighttime warm bias. This is due to a poor representation of the steep slopes on this side of the basin. Basin stations where the terrain is better represented by the model have a distinct warm, moist bias at night. Stations in snow-covered areas have a cold bias for both day and night. Biases are not dependent on forecast lead or validation time. Several potential causes for the various errors are considered in a series of sensitivity experiments. An experiment with 4-km grid spacing, which better resolves the gradient of the slopes on the east side of the basin, yields smaller errors along the east corridor of the basin. The NAM assumes all soil water freezes at a temperature of 273 K. This is likely not representative of the freezing temperature in the salt flats in the western part of the basin, since salt reduces the freezing point of water. An experiment testing this hypothesis shows that reducing the freezing point of soil water in the salt flats leads to an average error reduction between 1.5 and 4 K, depending on the station and time of day. Using a planetary boundary layer scheme that has greater mixing alleviates the cold bias over snow somewhat, but the exact source of this bias could not be determined.