bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coxsackievirus A24 Variant Uses Sialic Acid-Containing
O
-Linked Glycoconjugates as Cellular Receptors on Human Ocular Cells
Authors: Mistry Nitesh , Inoue Hirotoshi , Jamshidi Fariba , Storm Rickard J. , Oberste M. Steven , Arnberg Niklas 
Published: September 2011

ABSTRACT

Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection. Previously it has been suggested that CVA24v uses sialic acid-containing glycoconjugates as attachment receptors on corneal cells, but the nature of these receptors is poorly described. Here, we set out to characterize and identify the cellular components serving as receptors for CVA24v. Binding and infection experiments using corneal cells treated with deglycosylating enzymes or metabolic inhibitors of
de novo
glycosylation suggested that the receptor(s) used by CVA24v are constituted by sialylated
O
-linked glycans that are linked to one or more cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock-transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v. Finally, binding competition experiments using a library of mono- and oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to Neu5Acα2,3Gal disaccharides (Neu5Ac is
N
-acetylneuraminic acid). These results provide further insights into the early steps of the CVA24v life cycle.
A Physical Link between the Pseudorabies Virus Capsid and the Nuclear Egress Complex
Authors: Leelawong Mindy , Guo Dongsheng , Smith Gregory A. 
Published: September 2011

ABSTRACT
Following their assembly, herpesvirus capsids exit the nucleus by budding at the inner nuclear membrane. Two highly conserved viral proteins are required for this process, pUL31 and pUL34. In this report, we demonstrate that the pUL31 component of the pseudorabies virus nuclear egress complex is a conditional capsid-binding protein that is unmasked in the absence of pUL34. The interaction between pUL31 and capsids was confirmed through fluorescence microscopy and Western blot analysis of purified intranuclear capsids. Three viral proteins were tested for their abilities to mediate the pUL31-capsid interaction: the minor capsid protein pUL25, the portal protein pUL6, and the terminase subunit pUL33. Despite the requirement for each protein in nuclear egress, none of these viral proteins were required for the pUL31-capsid interaction. These findings provide the first formal evidence that a herpesvirus nuclear egress complex interacts with capsids and have implications for how DNA-containing capsids are selectively targeted for nuclear egress.
Role of the Two Sialic Acid Binding Sites on the Newcastle Disease Virus HN Protein in Triggering the Interaction with the F Protein Required for the Promotion of Fusion
Authors: Mahon Paul J. , Mirza Anne M. , Iorio Ronald M. 
Published: September 2011

ABSTRACT
Newcastle disease virus (NDV)-induced membrane fusion requires an interaction between the hemagglutinin-neuraminidase (HN) attachment and the fusion (F) proteins, triggered by HN′s binding to receptors. NDV HN has two sialic acid binding sites: site I, which also mediates neuraminidase activity, and site II, which straddles the membrane-distal end of the dimer interface. By characterizing the effect on receptor binding avidity and F-interactive capability of HN dimer interface mutations, we present evidence consistent with (i) receptor engagement by site I triggering the interaction with F and (ii) site II functioning to maintain high-avidity receptor binding during the fusion process.
The Encapsidated Genome of Microplitis demolitor Bracovirus Integrates into the Host Pseudoplusia includens
Authors: Beck Markus H. , Zhang Shu , Bitra Kavita , Burke Gaelen R. , Strand Michael R. 
Published: September 2011

ABSTRACT

Polydnaviruses (PDVs) are symbionts of parasitoid wasps that function as gene delivery vehicles in the insects (hosts) that the wasps parasitize. PDVs persist in wasps as integrated proviruses but are packaged as circularized and segmented double-stranded DNAs into the virions that wasps inject into hosts. In contrast, little is known about how PDV genomic DNAs persist in host cells.
Microplitis demolitor
carries
Microplitis demolitor
bracovirus (MdBV) and parasitizes the host
Pseudoplusia includens
. MdBV infects primarily host hemocytes and also infects a hemocyte-derived cell line from
P. includens
called CiE1 cells. Here we report that all 15 genomic segments of the MdBV encapsidated genome exhibited long-term persistence in CiE1 cells. Most MdBV genes expressed in hemocytes were persistently expressed in CiE1 cells, including members of the
glc
gene family whose products transformed CiE1 cells into a suspension culture. PCR-based integration assays combined with cloning and sequencing of host-virus junctions confirmed that genomic segments J and C persisted in CiE1 cells by integration. These genomic DNAs also rapidly integrated into parasitized
P. includens
. Sequence analysis of wasp-viral junction clones showed that the integration of proviral segments in
M. demolitor
was associated with a wasp excision/integration motif (WIM) known from other bracoviruses. However, integration into host cells occurred in association with a previously unknown domain that we named the host integration motif (HIM). The presence of HIMs in most MdBV genomic DNAs suggests that the integration of each genomic segment into host cells occurs through a shared mechanism.
The M Segment of the 2009 New Pandemic H1N1 Influenza Virus Is Critical for Its High Transmission Efficiency in the Guinea Pig Model
Authors: Chou Yi-ying , Albrecht Randy A. , Pica Natalie , Lowen Anice C. , Richt Jürgen A. , García-Sastre Adolfo , Palese Peter , Hai Rong 
Published: September 2011

ABSTRACT
A remarkable feature of the 2009 pandemic H1N1 influenza virus is its efficient transmissibility in humans compared to that of precursor strains from the triple-reassortant swine influenza virus lineage, which cause only sporadic infections in humans. The viral components essential for this phenotype have not been fully elucidated. In this study, we aimed to determine the viral factors critical for aerosol transmission of the 2009 pandemic virus. Single or multiple segment reassortments were made between the pandemic A/California/04/09 (H1N1) (Cal/09) virus and another H1N1 strain, A/Puerto Rico/8/34 (H1N1) (PR8). These viruses were then tested in the guinea pig model to understand which segment of Cal/09 virus conferred transmissibility to the poorly transmissible PR8 virus. We confirmed our findings by generating recombinant A/swine/Texas/1998 (H3N2) (sw/Tx/98) virus, a representative triple-reassortant swine virus, containing segments of the Cal/09 virus. The data showed that the M segment of the Cal/09 virus promoted aerosol transmissibility to recombinant viruses with PR8 and sw/Tx/98 virus backgrounds, suggesting that the M segment is a critical factor supporting the transmission of the 2009 pandemic virus.
A Conserved Peptide in West Nile Virus NS4A Protein Contributes to Proteolytic Processing and Is Essential for Replication
Authors: Ambrose R. L. , Mackenzie J. M. 
Published: September 2011

ABSTRACT

The West Nile virus strain Kunjin virus (WNV
KUN
) NS4A protein is a multifunctional protein involved in membrane proliferation, stimulation of cellular pathways, and evasion of host defense and is a major component of the WNV
KUN
RNA replication complex. We identified a highly conserved region (
120
P-E-P-E
123
) upstream of the viral protease dibasic cleavage site and investigated whether this motif was required for WNV
KUN
replication. Single point mutations to alanine and a PEPE deletion mutation were created in a full-length infectious WNV
KUN
molecular clone. All mutations drastically impaired viral replication and virion production, except that of the P122A mutant, which was slightly attenuated. These mutations were subsequently transferred to a WNV
KUN
replicon to specifically assess effects on RNA replication alone. Again, all mutants, except P122A, showed severely reduced negative-sense RNA production as well as decreased viral protein production. Correspondingly, immunofluorescence analyses showed a lack of double-stranded RNA (dsRNA) labeling and a dispersed localization of the WNV
KUN
proteins, suggesting that replication complex formation was additionally impaired. Attempts to rescue replication via conservative mutants largely failed except for substitution of Asp at E121, suggesting that a negative charge at this residue is equally important. Analysis of viral protein processing suggested that cleavage of the 2K peptide from NS4A did not occur with the mutant constructs. These observations imply that the combined effects of proline and negatively charged residues within the PEPE peptide are essential to promote the cleavage of 2K from NS4A, which is a prerequisite for efficient WNV replication.
Molecular Mechanism of Scanning and Start Codon Selection in Eukaryotes
Authors: Hinnebusch Alan G. 
Published: September 2011

SUMMARY

The correct translation of mRNA depends critically on the ability to initiate at the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the 5′ end of the mRNA and then inspects the leader base by base for an AUG in a suitable context, using complementarity with the anticodon of methionyl initiator tRNA (Met-tRNA
i
Met
) as the key means of identifying AUG. Over the past decade, a combination of yeast genetics, biochemical analysis in reconstituted systems, and structural biology has enabled great progress in deciphering the mechanism of ribosomal scanning. A robust molecular model now exists, describing the roles of initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in stabilizing an “open” conformation of the 40S subunit with Met-tRNA
i
Met
bound in a low-affinity state conducive to scanning and in triggering rearrangement into a “closed” conformation incompatible with scanning, which features Met-tRNA
i
Met
more tightly bound to the “P” site and base paired with AUG. It has also emerged that multiple DEAD-box RNA helicases participate in producing a single-stranded “landing pad” for the 40S subunit and in removing the secondary structure to enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded form for base-by-base inspection in the P site.
Use of geophysical methods for soil profile evaluation
Authors: Groves Paul , Cascante Giovanni , Dundas Dave , Chatterji P.K. 
Published: September 2011

A geophysical investigation was performed to evaluate the effectiveness of three geophysical methods (electrical resistivity imaging (ERI), seismic refraction (SR), and multiple-channel analysis of surface waves (MASW)) for geotechnical site characterization in swamps and environmentally sensitive wetland areas. The geophysical test results were verified against the results from borehole and cone penetrometer test logs. The ERI results were best for determining the depth to the glacial till. However, the resolution of the ERI survey was not sufficient to accurately predict the upper lithologies. The electrode spacing (4 m) was instead selected to reliably predict the depth to the till, which in this case varied between 4.6 and 10.7 m. The SR results overestimated the depth to the till because of the presence of a stiffness reversal. The MASW results predicted the depth to the refusal till layer less accurately than the ERI method. However, this method was able to detect the three distinct layers above the till, even though the layer thicknesses were consistently underestimated. The complementary use of geophysical techniques was a successful approach in determining the main soil units and the depth to the competent layer (till) at the site. These methods can be used as a basis for further development to optimize a procedure to reduce the number of boreholes required for conventional site investigations in areas that are environmentally sensitive or where access is restricted.
Growth dynamics of black spruce in stands located between the 51st and 52nd parallels in the boreal forest of Quebec, Canada
Authors: Tremblay Marie-Josée , Rossi Sergio , Morin Hubert 
Published: September 2011

Despite their ecological importance, the role and effects of insect outbreaks on stand dynamics of the northern boreal forests in North America have still to be demonstrated. The study was conducted between the 51st and 52nd parallels in Quebec, Canada, to identify mechanisms governing regeneration of high-latitude stands by investigating variations in growth of trees during stand development. Chronologies of tree-ring width and individual dynamics of growth in height and volume were assessed in black spruce ( Picea mariana (Mill.) B.S.P) of one even-aged and five uneven-aged stands. Uneven-aged stands contained trees up to 340 years old and representing almost every age class. Several growth reductions were observed that were synchronized between stands and were characterized by high amplitudes but different percentages of affected trees. These reductions were followed by marked growth releases. Even if the absence of nonhost species prevented the building of chronologies that could confirm the origin of growth reductions, the findings suggested that spruce budworm ( Archips fumiferana Clemens [syn.: Choristoneura fumiferana (Clemens)]) outbreaks contribute to the formation and maintenance of the uneven-aged structure of older black spruce stands at high latitudes.
Toward a definition of the range of variability of central European mixedFagus–Abies–Piceaforests: the nearly steady-state forest of Lom (Bosnia and Herzegovina)
Authors: Motta Renzo , Berretti Roberta , Castagneri Daniele , Dukić Vojislav , Garbarino Matteo , Govedar Zoran , Lingua Emanuele , Maunaga Zoran , Meloni Fabio 
Published: September 2011

Knowledge on the range of variability of montane European forests is hampered by limited data on the natural disturbance regime and by the small size of old-growth remnants. We studied the mixed Fagus – Abies – Picea Lom forest reserve (55.8 ha) in Bosnia and Herzegovina at three different scales: a grid of 40 sampling points to describe the structural characteristics and their range of variability, three transects to analyse gap size and gap fraction, and a 1.1 ha permanent plot to reconstruct age structure and disturbance history. The forest is characterized by a high volume of living trees (763 m3·ha–1in the 55.8 ha core area and 1160 m3·ha–1in the permanent plot) and of coarse woody debris (327 and 383 m3·ha–1, respectively). The percentages of forest area in canopy and expanded gaps are 19% and 41%, respectively. The median canopy gap size is 76.9 m2and ranges from 11.1 to 708.0 m2. There are large (up to 120 cm diameter at breast height) and very old trees (441, 432, and 416 years for silver fir ( Abies alba Mill.), Norway spruce ( Picea abies (L.) Karst.), and European beech ( Fagus sylvatica L.), respectively). During the last three centuries, the disturbance patterns have been characterized by single-tree or small group mortality. In central Europe, this forest is at the end of a gradient from forests characterized by intermediate disturbances to those where very small-scale processes predominate.
Comparison of Continuous versus Categorical Tumor Measurement–Based Metrics to Predict Overall Survival in Cancer Treatment Trials
Authors: An Ming-Wen , Mandrekar Sumithra J. , Branda Megan E. , Hillman Shauna L. , Adjei Alex A. , Pitot Henry C. , Goldberg Richard M. , Sargent Daniel J. 
Published: September 2011

Abstract
Purpose: The categorical definition of response assessed via the Response Evaluation Criteria in Solid Tumors has documented limitations. We sought to identify alternative metrics for tumor response that improve prediction of overall survival.
Experimental Design: Individual patient data from three North Central Cancer Treatment Group trials (N0026, n = 117; N9741, n = 1,109; and N9841, n = 332) were used. Continuous metrics of tumor size based on longitudinal tumor measurements were considered in addition to a trichotomized response [TriTR: response (complete or partial) vs. stable disease vs. progression). Cox proportional hazards models, adjusted for treatment arm and baseline tumor burden, were used to assess the impact of the metrics on subsequent overall survival, using a landmark analysis approach at 12, 16, and 24 weeks postbaseline. Model discrimination was evaluated by the concordance (c) index.
Results: The overall best response rates for the three trials were 26%, 45%, and 25%, respectively. Although nearly all metrics were statistically significantly associated with overall survival at the different landmark time points, the concordance indices (c-index) for the traditional response metrics ranged from 0.59 to 0.65; for the continuous metrics from 0.60 to 0.66; and for the TriTR metrics from 0.64 to 0.69. The c-indices for TriTR at 12 weeks were comparable with those at 16 and 24 weeks.
Conclusions: Continuous tumor measurement–based metrics provided no predictive improvement over traditional response–based metrics or TriTR; TriTR had better predictive ability than best TriTR or confirmed response. If confirmed, TriTR represents a promising endpoint for future phase II trials. Clin Cancer Res; 17(20); 6592–9. ©2011 AACR.
Aflibercept (VEGF Trap) in Inoperable Stage III or Stage IV Melanoma of Cutaneous or Uveal Origin
Authors: Tarhini Ahmad A. , Frankel Paul , Margolin Kim A. , Christensen Scott , Ruel Christopher , Shipe-Spotloe Janice , Gandara David R. , Chen Alice , Kirkwood John M. 
Published: September 2011

Abstract
Purpose: Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor with potent preclinical antitumor activity in melanoma. We conducted a multicenter phase II study in patients with inoperable stage III or IV melanoma and no prior chemotherapy.
Experimental Design: A two-stage design was adopted to evaluate 4-month progression-free survival rate (PFSR) and response rate. Aflibercept was given at 4 mg/kg intravenously every 2 weeks. Response was assessed every 8 weeks. First-stage accrual of 21 patients was specified and with an adequate 4-month PFSR accrual continued to a total of 41.
Results: Forty-one patients of ages 23 to 84 (median = 57) were enrolled. Thirty-nine had American Joint Committee on Cancer stage IV (5 M1a, 7 M1b, and 27 M1c) and 2 had inoperable stage IIIC (N3). Eastern Cooperative Oncology Group (ECOG) performance status was 0 (27 patients) or 1 (14 patients). Ten patients had primary uveal melanoma, 28 cutaneous, and 3 had unknown primaries. A median of 7 cycles were initiated (range: 1–56). Grade 3 and 4 toxicities included hypertension in 9 patients (22%) and proteinuria in 6 (15%). Among 40 patients evaluable for efficacy (those who initiated aflibercept), 3 (7.5%) had a confirmed partial response and 20 had progression-free survival of 4 months or above. The predicted 1-year survival rate derived from the Korn meta-analysis model is 36% (N = 39), whereas we observed a corresponding 56.4% survival rate at 1 year (95% CI, 43–74, P &lt; 0.005). Median overall survival in this trial is 16.3 months (95% CI, 9.2 to not reached). We observed a significant association between severity of hypertension following aflibercept and survival improvement.
Conclusions: Aflibercept showed promising activity in patients with metastatic melanoma of cutaneous or uveal origin. Further evaluation of aflibercept as a single agent and in combination is warranted. Clin Cancer Res; 17(20); 6574–81. ©2011 AACR.
A Randomized Controlled Trial of Celecoxib to Prevent Recurrence of Nonmuscle-Invasive Bladder Cancer
Authors: Sabichi Anita L. , Lee J. Jack , Grossman H. Barton , Liu Suyu , Richmond Ellen , Czerniak Bogdan A. , De la Cerda Jorge , Eagle Craig , Viner Jaye L. , Palmer J. Lynn , Lerner Seth P. 
Published: September 2011

Abstract
Significant morbidity and expense result from frequent recurrences of nonmuscle-invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ (Tis) is a poor prognostic factor. Predicated on observational and preclinical data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized, double-blind, placebo-controlled trial to determine whether celecoxib could reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for recurrence. A total of 146 patients were randomized to celecoxib (200 mg) or placebo orally twice daily for at least 12 months. The average treatment duration was 1.25 years. Primary intent-to-treat analysis revealed celecoxib did not statistically significantly prolong TTR compared with placebo (P = 0.17, log rank) with a median follow-up of 2.49 years. The recurrence-free rate at 12 months with celecoxib was 88% (95% CI: 0.81–0.96) versus 78% (95% CI: 0.69–0.89) with placebo. After controlling for covariates with Cox regression analysis, recurrence rates did not differ between the two study arms (HR = 0.69; 95% CI: 0.37–1.29). However, celecoxib had a marginally significant effect on reducing metachronous recurrences (vs. placebo) with HR of 0.56 (95% CI: 0.3–1.06; P = 0.075). Celecoxib was well tolerated, with similar adverse events and quality-of-life in both arms. Our clinical trial results do not show a clinical benefit for celecoxib in preventing NMIBC recurrence but further investigation of COX-2 inhibitors in this setting is warranted. Cancer Prev Res; 4(10); 1580–9. ©2011 AACR.
Integration of 3D Electroanatomic Maps and Magnetic Resonance Scar Characterization Into the Navigation System to Guide Ventricular Tachycardia Ablation
Authors: Andreu David , Berruezo Antonio , Ortiz-Pérez José T. , Silva Etelvino , Mont Lluis , Borràs Roger , de Caralt Teresa María , Perea Rosario Jesús , Fernández-Armenta Juan , Zeljko Hrvojka , Brugada Josep 
Published: September 2011

Background—
Scar heterogeneity identified with contrast-enhanced cardiac magnetic resonance (CE-CMR) has been related to its arrhythmogenic potential by using different algorithms. The purpose of the study was to identify the algorithm that best fits with the electroanatomic voltage maps (EAM) to guide ventricular tachycardia (VT) ablation.

Methods and Results—

Three-dimensional scar reconstructions from preprocedural CE-CMR study at 3T were obtained and compared with EAMs of 10 ischemic patients submitted for a VT ablation. Three-dimensional scar reconstructions were created for the core (3D-CORE) and border zone (3D-BZ), applying cutoff values of 50%, 60%, and 70% of the maximum pixel signal intensity to discriminate between core and BZ. The left ventricular cavity from CE-CMR (3D-LV) was merged with the EAM, and the 3D-CORE and 3D-BZ were compared with the corresponding EAM areas defined with standard cutoff voltage values. The best match was obtained when a cutoff value of 60% of the maximum pixel signal intensity was used, both for core (
r
2
=0.827;
P
<0.001) and BZ (
r
2
=0.511;
P
=0.020), identifying 69% of conducting channels (CC) observed in the EAM. Matching improved when only the subendocardial half of the wall was segmented (CORE:
r
2
=0.808;
P
<0.001 and BZ:
r
2
=0.485;
P
=0.025), identifying 81% of CC. When comparing the location of each bipolar voltage intracardiac electrogram with respect to the 3D CE-CMR–derived structures, a Cohen κ coefficient of 0.70 was obtained.

Conclusions—
Scar characterization by means of high resolution CE-CMR resembles that of EAM and can be integrated into the CARTO system to guide VT ablation.