bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates
Authors: Li Xiao-Feng , Deng Yong-Qiang , Yang Hui-Qiang , Zhao Hui , Jiang Tao , Yu Xue-Dong , Li Shi-Hua , Ye Qing , Zhu Shun-Ya , Wang Hong-Jiang , Zhang Yu , Ma Jie , Yu Yong-Xin , Liu Zhong-Yu , Li Yu-Hua , Qin E-De , Shi Pei-Yong , Qin Cheng-Feng 
Published: October 2013

ABSTRACT
The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with ChinDENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.
Standard Trivalent Influenza Virus Protein Vaccination Does Not Prime Antibody-Dependent Cellular Cytotoxicity in Macaques
Authors: Jegaskanda Sinthujan , Amarasena Thakshila H. , Laurie Karen L. , Tan Hyon-Xhi , Butler Jeff , Parsons Matthew S. , Alcantara Sheilajen , Petravic Janka , Davenport Miles P. , Hurt Aeron C. , Reading Patrick C. , Kent Stephen J. 
Published: October 2013

ABSTRACTYearly vaccination with the trivalent inactivated influenza vaccine (TIV) is recommended, since current vaccines induce little cross neutralization to divergent influenza strains. Whether the TIV can induce antibody-dependent cellular cytotoxicity (ADCC) responses that can cross-recognize divergent influenza virus strains is unknown. We immunized 6 influenza-naive pigtail macaques twice with the 2011–2012 season TIV and then challenged the macaques, along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza virus-specific CD8 T cell (CTL) responses using a sensitive major histocompatibility complex (MHC) tetramer reagent. The TIV was weakly immunogenic and, although binding antibodies were detected by enzyme-linked immunosorbent assay (ELISA), did not induce detectable influenza virus-specific ADCC or CTL responses. The H1N1 challenge elicited robust ADCC to both homologous and heterologous H1 HA proteins, but not influenza virus HA proteins from different subtypes (H2 to H7). There was no anamnestic influenza virus-specific ADCC or CTL response in vaccinated animals. The subsequent H3N2 challenge did not induce or boost ADCC either to H1 HA proteins or to divergent H3 proteins but did boost CTL responses. ADCC or CTL responses were not induced by TIV vaccination in influenza-naive macaques. There was a marked difference in the ability of infection compared to that of vaccination to induce cross-reactive ADCC and CTL responses. Improved vaccination strategies are needed to induce broad-based ADCC immunity to influenza.
Simian Foamy Virus Infection of Rhesus Macaques in Bangladesh: Relationship of Latent Proviruses and Transcriptionally Active Viruses
Authors: Soliven Khanh , Wang Xiaoxing , Small Christopher T. , Feeroz Mostafa M. , Lee Eun-Gyung , Craig Karen L. , Hasan Kamrul , Engel Gregory A. , Jones-Engel Lisa , Matsen Frederick A. , Linial Maxine L. 
Published: October 2013

ABSTRACT

Simian foamy viruses (SFV) are complex retroviruses that are ubiquitous in nonhuman primates (NHP) and are zoonotically transmitted to humans, presumably through NHP saliva, by licking, biting, and other behaviors. We have studied SFV in free-ranging rhesus macaques in Bangladesh. It has been previously shown that SFV in immunocompetent animals replicates to detectable levels only in superficial epithelial cells of the oral mucosa, although latent proviruses are found in most, if not all, tissues. In this study, we compare DNA sequences from latent SFV proviruses found in blood cells of 30 Bangladesh rhesus macaques to RNA sequences of transcriptionally active SFV from buccal swabs obtained from the same animals. Viral strains, defined by differences in SFV
gag
sequences, from buccal mucosal specimens overlapped with those from blood samples in 90% of animals. Thus, latent proviruses in peripheral blood mononuclear cells (PBMC) are, to a great extent, representative of viruses likely to be transmitted to other hosts. The level of SFV RNA in buccal swabs varied greatly between macaques, with increasing amounts of viral RNA in older animals. Evidence of APOBEC3-induced mutations was found in
gag
sequences derived from the blood and oral mucosa.
Truncation and Sequence Shuffling of Segment 6 Generate Replication-Competent Neuraminidase-Negative Influenza H5N1 Viruses
Authors: Kalthoff Donata , Röhrs Susanne , Höper Dirk , Hoffmann Bernd , Bogs Jessica , Stech Jürgen , Beer Martin 
Published: October 2013

ABSTRACT
Influenza viruses are highly genetically variable and escape from immunogenic pressure by antigenic changes in their surface proteins, referred to as “antigenic drift” and “antigenic shift.” To assess the potential genetic plasticity under strong selection pressure, highly pathogenic avian influenza virus (HPAIV) of subtype H5N1 was passaged 50 times in embryonated chicken eggs in the presence of a neutralizing, polyclonal chicken serum. The resulting mutant acquired major alterations in the neuraminidase (NA)-encoding segment. Extensive deletions and rearrangements were detected, in contrast to only 12 amino acid substitutions within all other segments. Interestingly, this new neuraminidase segment resulted from complex sequence shuffling and insertion of a short fragment originating from the PA segment. Characterization of that novel variant revealed a loss of the neuraminidase protein and enzymatic activity, but its replication efficiency remained comparable to that of the wild type. Using reverse genetics, a recombinant virus consisting of the wild-type backbone and the shortened NA segment could be generated; however, generation of this recombinant virus required the polybasic hemagglutinin cleavage site. Two independent repetitions starting with egg passage 30 in the presence of alternative chicken-derived immune sera selected mutants with similar but different large deletions within the NA segment without any neuraminidase activity, indicating a general mechanism. In chicken, these virus variants were avirulent, even though the HPAIV polybasic hemagglutinin cleavage site was still present. Overall, the variants reported here are the first HPAIV H5N1 strains without a functional neuraminidase shown to grow efficiently without any helper factor. These novel HPAIV variants may facilitate future studies shedding light on the role of neuraminidase in virus replication and pathogenicity.
Next-Generation Sequence Analysis of the Genome of RFHVMn, the Macaque Homolog of Kaposi's Sarcoma (KS)-Associated Herpesvirus, from a KS-Like Tumor of a Pig-Tailed Macaque
Authors: Bruce A. Gregory , Ryan Jonathan T. , Thomas Mathew J. , Peng Xinxia , Grundhoff Adam , Tsai Che-Chung , Rose Timothy M. 
Published: October 2013

ABSTRACT

The complete sequence of retroperitoneal fibromatosis-associated herpesvirus
Macaca nemestrina
(RFHVMn), the pig-tailed macaque homolog of Kaposi's sarcoma-associated herpesvirus (KSHV), was determined by next-generation sequence analysis of a Kaposi's sarcoma (KS)-like macaque tumor. Colinearity of genes was observed with the KSHV genome, and the core herpesvirus genes had strong sequence homology to the corresponding KSHV genes. RFHVMn lacked homologs of open reading frame 11 (ORF11) and KSHV ORFs K5 and K6, which appear to have been generated by duplication of ORFs K3 and K4 after the divergence of KSHV and RFHV. RFHVMn contained positional homologs of all other unique KSHV genes, although some showed limited sequence similarity. RFHVMn contained a number of candidate microRNA genes. Although there was little sequence similarity with KSHV microRNAs, one candidate contained the same seed sequence as the positional homolog, kshv-miR-K12-10a, suggesting functional overlap. RNA transcript splicing was highly conserved between RFHVMn and KSHV, and strong sequence conservation was noted in specific promoters and putative origins of replication, predicting important functional similarities. Sequence comparisons indicated that RFHVMn and KSHV developed in long-term synchrony with the evolution of their hosts, and both viruses phylogenetically group within the RV1 lineage of Old World primate rhadinoviruses. RFHVMn is the closest homolog of KSHV to be completely sequenced and the first sequenced RV1 rhadinovirus homolog of KSHV from a nonhuman Old World primate. The strong genetic and sequence similarity between RFHVMn and KSHV, coupled with similarities in biology and pathology, demonstrate that RFHVMn infection in macaques offers an important and relevant model for the study of KSHV in humans.
CpG Dinucleotide Frequencies Reveal the Role of Host Methylation Capabilities in Parvovirus Evolution
Authors: Upadhyay Mohita , Samal Jasmine , Kandpal Manish , Vasaikar Suhas , Biswas Banhi , Gomes James , Vivekanandan Perumal 
Published: October 2013

ABSTRACT
Parvoviruses are rapidly evolving viruses that infect a wide range of hosts, including vertebrates and invertebrates. Extensive methylation of the parvovirus genome has been recently demonstrated. A global pattern of methylation of CpG dinucleotides is seen in vertebrate genomes, compared to “fractional” methylation patterns in invertebrate genomes. It remains unknown if the loss of CpG dinucleotides occurs in all viruses of a given DNA virus family that infect host species spanning across vertebrates and invertebrates. We investigated the link between the extent of CpG dinucleotide depletion among autonomous parvoviruses and the evolutionary lineage of the infected host. We demonstrate major differences in the relative abundance of CpG dinucleotides among autonomous parvoviruses which share similar genome organization and common ancestry, depending on the infected host species. Parvoviruses infecting vertebrate hosts had significantly lower relative abundance of CpG dinucleotides than parvoviruses infecting invertebrate hosts. The strong correlation of CpG dinucleotide depletion with the gain in TpG/CpA dinucleotides and the loss of TpA dinucleotides among parvoviruses suggests a major role for CpG methylation in the evolution of parvoviruses. Our data present evidence that links the relative abundance of CpG dinucleotides in parvoviruses to the methylation capabilities of the infected host. In sum, our findings support a novel perspective of host-driven evolution among autonomous parvoviruses.
The Nuclear-Cytoplasmic Shuttling of Virion Host Shutoff RNase Is Enabled by pU
L
47 and an Embedded Nuclear Export Signal and Defines the Sites of Degradation of AU-Rich and Stable Cellular mRNAs
Authors: Shu Minfeng , Taddeo Brunella , Roizman Bernard 
Published: October 2013

ABSTRACT

The herpes simplex virus host shutoff RNase (VHS-RNase) is the major early block of host responses to infection. VHS-RNase is introduced into cells during infection and selectively degrades stable mRNAs made before infection and the normally short-lived AU-rich stress response mRNAs induced by sensors of innate immunity. Through its interactions with pU
L
47, another tegument protein, it spares from degradation viral mRNAs. Analyses of embedded motifs revealed that VHS-RNase contains a nuclear export signal (NES) but not a nuclear localization signal. To reconcile the potential nuclear localization with earlier studies showing that VHS-RNase degrades mRNAs in polyribosomes, we constructed a mutant in which NES was ablated. Comparison of the mutant and wild-type VHS-RNases revealed the following. (i) On infection, VHS-RNase is transported to the nucleus, but only the wild-type protein shuttles between the nucleus and cytoplasm. (ii) Both VHS-RNases localized in the cytoplasm following transfection. On cotransfection with pU
L
47, a fraction of VHS-RNase was translocated to the nucleus, suggesting that pU
L
47 may enable nuclear localization of VHS-RNase. (iii) In infected cells, VHS-RNase lacking NES degraded the short-lived AU-rich mRNAs but not the stable mRNAs. In transfected cells, both wild-type and NES mutant VHS-RNases effectively degraded cellular mRNAs. Our results suggest that the stable mRNAs are degraded in the cytoplasm, whereas the AU-rich mRNAs may be degraded in both cellular compartments. The selective sparing of viral mRNAs may take place during the nuclear phase in the course of interaction of pU
L
47, VHS-RNase, and nascent viral mRNAs.
Geology and U–Pb geochronology of the Espedalen Complex, southern Norway, and its position in the Caledonian nappe systems
Authors: Corfu F. , Heim M. 
Published: October 2013

Abstract
The Espedalen Nappe is located in the east of the Jotun–Valdres Nappe Complex in southern Norway. Its main component, the Espedalen Complex, consists of an early suite of jotunite, charnockite and augengneiss, a main anorthosite–ultramafite–norite suite, and a late gabbronorite suite. Mafic dykes and lamprophyres cut the complex, some being feeders to the Stylskampen mafic to felsic suite at the western margin of the complex. The complex hosts Ni–Cu mineralizations which were mined in past centuries. Two crystalline outliers occur at Ormtjernkampen and Røssjøkollen further south. Caledonian convergence thrust the nappe on to Early Palaeozoic sedimentary rocks. Rocks of the Espedalen Complex are covered and/or tectonically interleaved with Late Precambrian conglomerates and arkoses of the Valdres Group. Dating of zircon and titanite by ID-TIMS U–Pb indicates formation of the complex at 1520–1510 Ma, followed by deformation and metamorphism between 1050 and 950 Ma during the Sveconorwegian orogeny, before the eventual translation during the Caledonian orogeny. These data indicate an affinity of the nappe with Telemarkian crust in the autochthonous Baltic basement, in contrast to the rocks of the overlying Jotun Complex which correlate instead to Gothian crust formed between 1600 and 1700 Ma.
ERK1/2 Blockade Prevents Epithelial–Mesenchymal Transition in Lung Cancer Cells and Promotes Their Sensitivity to EGFR Inhibition
Authors: Buonato Janine M. , Lazzara Matthew J. 
Published: October 2013

Abstract
Overcoming cellular mechanisms of de novo and acquired resistance to drug therapy remains a central challenge in the clinical management of many cancers, including non–small cell lung cancer (NSCLC). Although much work has linked the epithelial–mesenchymal transition (EMT) in cancer cells to the emergence of drug resistance, it is less clear where tractable routes may exist to reverse or inhibit EMT as a strategy for drug sensitization. Here, we demonstrate that extracellular signal-regulated kinase (ERK) 1/2 (mitogen-activated protein kinase 3/1, MAPK3/1) signaling plays a key role in directing the mesenchymal character of NSCLC cells and that blocking ERK signaling is sufficient to heighten therapeutic responses to EGF receptor (EGFR) inhibitors. MEK1/2 (MAPKK1/2) inhibition promoted an epithelial phenotype in NSCLC cells, preventing induction of EMT by exogenous TGF-β. Moreover, in cells exhibiting de novo or acquired resistance to the EGFR inhibitor gefitinib, MEK inhibition enhanced the sensitivity to gefitinib and slowed cell migration. These effects only occurred, however, if MEK was inhibited for a period sufficient to trigger changes in EMT marker expression. Consistent with these findings, changes in EMT phenotypes and markers were also induced by the expression of mutant KRAS in a MEK-dependent manner. Our results suggest that prolonged exposure to MEK or ERK inhibitors may not only restrain EMT but also overcome naïve or acquired resistance of NSCLC to EGFR-targeted therapy in the clinic. Cancer Res; 74(1); 309–19. ©2013 AACR.
Unsupervised Event Coreference Resolution
Authors: Bejan Cosmin , Harabagiu Sanda 
Published: October 2013

The task of event coreference resolution plays a critical role in many natural language processing applications such as information extraction, question answering, and topic detection and tracking. In this article, we describe a new class of unsupervised, nonparametric Bayesian models with the purpose of probabilistically inferring coreference clusters of event mentions from a collection of unlabeled documents. In order to infer these clusters, we automatically extract various lexical, syntactic, and semantic features for each event mention from the document collection. Extracting a rich set of features for each event mention allows us to cast event coreference resolution as the task of grouping together the mentions that share the same features (they have the same participating entities, share the same location, happen at the same time, etc.). Some of the most important challenges posed by the resolution of event coreference in an unsupervised way stem from (a) the choice of representing event mentions through a rich set of features and (b) the ability of modeling events described both within the same document and across multiple documents. Our first unsupervised model that addresses these challenges is a generalization of the hierarchical Dirichlet process. This new extension presents the hierarchical Dirichlet process's ability to capture the uncertainty regarding the number of clustering components and, additionally, takes into account any finite number of features associated with each event mention. Furthermore, to overcome some of the limitations of this extension, we devised a new hybrid model, which combines an infinite latent class model with a discrete time series model. The main advantage of this hybrid model stands in its capability to automatically infer the number of features associated with each event mention from data and, at the same time, to perform an automatic selection of the most informative features for the task of event coreference. The evaluation performed for solving both within- and cross-document event coreference shows significant improvements of these models when compared against two baselines for this task.
The Death of David’s Son by Bathsheba (II Sam 12:13-25): A Narrative in Context
Authors: Jacobs Jonathan 
Published: October 2013

Abstract
The episode of David’s sin and his punishment (II Sam 11-12) represents a turning point in the description of David’s reign. While this dramatic episode has received extensive attention in biblical exegesis, the final section of the narrative, recording the death of Bathsheba’s son, has been largely neglected, with little attention to its contribution to the story.
In this article I propose that the main contribution of the story is its exposure of his inner world following the revelation of his sin by the prophet Nathan. The biblical narrative conveys its ideas in an indirect manner, through various literary devices. By means of analogies, discrepancies between descriptions, and secondary characters, the text hints at David’s process of repentance for his sin. We might say that David undergoes a process in two stages: Initially, immediately after the speech by the prophet Nathan, he demonstrates a repentance that is quick and spontaneous, but only partial. Thereafter he undergoes a process of slow and gradual repentance, in which he repairs all the levels of his sin.
Shelter availability influences social behavior and habitat choice in crayfish, Orconectes virilis
Authors: Fero Kandice C. , Moore Paul A. 
Published: October 2013

Conspecific distribution across differing microhabitats may arise due to individual differences in resource requirements, vulnerability to predation, environmental tolerances, and as a direct result of social interaction. The aim of this study was to examine crayfish distributions across habitats with varying resource availability and to examine whether such distributions are correlated with dominance relationships among individuals. Agonistic interactions, habitat use, and shelter use were observed in mixed-sex populations of eight crayfish, Orconectes virilis. Populations were placed in a semi-natural, 4 × 4 m arena for 20 h that was split into shelter-poor (low), shelter-rich (high) and shelter-free (free) areas. The presence of shelter was associated with a significant increase in crayfish habitat use. Overall agonism also increased in habitats where shelter was present. Status specific differences in shelter and habitat use were observed and were dependent upon environmental context (e.g., day versus night). Lower ranking crayfish were found to occupy and defend shelter less frequently than dominant crayfish and low ranking crayfish were also found more often in shelter-poor habitat. These status-specific differences in behavior were only observed during the day when shelter-related behaviors were increased overall. Distinct shelter use strategies were also apparent between top-ranked (alpha) and bottom-ranked (omega) crayfish. Taken together, these results suggest that shelter use and habitat use are, in part, mediated by social status. Additionally, these results indicate that habitat selection may arise as a consequence of status-specific differences in resource use.