bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modification of the Respiratory Syncytial Virus F Protein in Virus-Like Particles Impacts Generation of B Cell Memory
Authors: Schmidt Madelyn R. , McGinnes-Cullen Lori W. , Kenward Sarah A. , Willems Kristin N. , Woodland Robert T. , Morrison Trudy G. 
Published: June 2014

ABSTRACT
Immunization with virus-like particles (VLPs) containing the Newcastle disease virus (NDV) core proteins, NP and M, and two chimera proteins (F/F and H/G) containing the respiratory syncytial virus (RSV) F- and G-protein ectodomains fused to the transmembrane and cytoplasmic domains of NDV F and HN proteins, respectively, stimulated durable RSV-neutralizing antibodies, F-protein-specific long-lived, bone marrow-associated plasma cells (LLPCs), and B cell memory, in striking contrast to RSV infection, which did not (M. R. Schmidt, L. W. McGinnes, S. A. Kenward, K. N. Willems, R. T. Woodland, and T. G. Morrison, J. Virol. 86:11654–11662, 2012). Here we report the characterization of a VLP with an RSV F-protein ectodomain fused to the NDV F-protein heptad repeat 2 (HR2), transmembrane, and cytoplasmic domain sequences, creating a chimera with two tandem HR2 domains, one from the RSV F protein and the other from the NDV F-protein ectodomain (F/HR2F). The F/HR2F chimera protein was efficiently assembled into VLPs along with the H/G chimera protein. This VLP (VLP-H/G+F/HR2F) stimulated anti-F-protein and anti-G-protein IgG, durable RSV-neutralizing antibodies, and anti-RSV F-protein-secreting LLPCs. However, the subtypes of anti-F-protein IgG induced were different from those elicited by VLPs containing the F/F chimera (VLP-H/G+F/F). Most importantly, VLP-H/G+F/HR2F did not induce RSV F-protein-specific B cell memory, as shown by the adoptive transfer of B cells from immunized animals to immunodeficient animals. The VLP did, however, induce B cell memory specific to the RSV G protein. Thus, the form of the F protein has a direct role in inducing anti-F-protein B cell memory.

IMPORTANCE
The development of vaccines for respiratory syncytial virus (RSV) is hampered by a lack of a clear understanding of the requirements for eliciting protective as well as durable human immune responses to virus antigens. The results of this study indicate that the form of the RSV F protein has a direct and significant impact on the type of anti-F-protein IgG antibodies induced and the generation of F-protein-specific memory. Identification of the conformation of the RSV F protein that most effectively stimulates not only LLPCs and but also memory B cells will be important in the future development of RSV vaccines.
The ATR Signaling Pathway Is Disabled during Infection with the Parvovirus Minute Virus of Mice
Authors: Adeyemi Richard O. , Pintel David J. 
Published: June 2014

ABSTRACT
The ATR kinase has essential functions in maintenance of genome integrity in response to replication stress. ATR is recruited to RPA-coated single-stranded DNA at DNA damage sites via its interacting partner, ATRIP, which binds to the large subunit of RPA. ATR activation typically leads to activation of the Chk1 kinase among other substrates. We show here that, together with a number of other DNA repair proteins, both ATR and its associated protein, ATRIP, were recruited to viral nuclear replication compartments (autonomous parvovirus-associated replication [APAR] bodies) during replication of the single-stranded parvovirus minute virus of mice (MVM). Chk1, however, was not activated during MVM infection even though viral genomes bearing bound RPA, normally a potent trigger of ATR activation, accumulate in APAR bodies. Failure to activate Chk1 in response to MVM infection was likely due to our observation that Rad9 failed to associate with chromatin at MVM APAR bodies. Additionally, early in infection, prior to the onset of the virus-induced DNA damage response (DDR), stalling of the replication of MVM genomes with hydroxyurea (HU) resulted in Chk1 phosphorylation in a virus dose-dependent manner. However, upon establishment of full viral replication, MVM infection prevented activation of Chk1 in response to HU and various other drug treatments. Finally, ATR phosphorylation became undetectable upon MVM infection, and although virus infection induced RPA32 phosphorylation on serine 33, an ATR-associated phosphorylation site, this phosphorylation event could not be prevented by ATR depletion or inhibition. Together our results suggest that MVM infection disables the ATR signaling pathway.

IMPORTANCE
Upon infection, the parvovirus MVM activates a cellular DNA damage response that governs virus-induced cell cycle arrest and is required for efficient virus replication. ATM and ATR are major cellular kinases that coordinate the DNA damage response to diverse DNA damage stimuli. Although a significant amount has been discovered about ATM activation during parvovirus infection, involvement of the ATR pathway has been less studied. During MVM infection, Chk1, a major downstream target of ATR, is not detectably phosphorylated even though viral genomes bearing the bound cellular single-strand binding protein RPA, normally a potent trigger of ATR activation, accumulate in viral replication centers. ATR phosphorylation also became undetectable. In addition, upon establishment of full viral replication, MVM infection prevented activation of Chk1 in response to hydroxyurea and various other drug treatments. Our results suggest that MVM infection disables this important cellular signaling pathway.
Identification and Characterization of Two Novel Spliced Genes Located in the
orf47-orf46-orf45
Gene Locus of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Chang Pey-Jium , Hung Chien-Hui , Wang Shie-Shan , Tsai Ping-Hsin , Shih Ying-Ju , Chen Li-Yu , Huang Hsiao-Yun , Wei Ling-Huei , Yen Ju-Bei , Lin Chun-Liang , Chen Lee-Wen 
Published: June 2014

ABSTRACT

The
orf47-orf46-orf45
gene cluster of Kaposi's sarcoma-associated herpesvirus (KSHV) is known to serially encode glycoprotein L (gL), uracil DNA glycosylase, and a viral tegument protein. Here, we identify two novel mRNA variants,
orf47/45-A
and
orf47/45-B
, alternatively spliced from a tricistronic
orf47-orf46-orf45
mRNA that is expressed in the
orf47-orf46-orf45
gene locus during the early stages of viral reactivation. The spliced gene products, ORF47/45-A and ORF47/45-B, consist of only a partial region of gL (ORF47), a unique 7-amino-acid motif, and the complete tegument protein ORF45. Like the ORF45 protein, ORF47/45-A and ORF47/45-B expressed in cells sufficiently activate the phosphorylation of p90 ribosomal S6 kinase (RSK) and extracellular signal-regulated protein kinase (ERK). However, unlike ORF45, both ORF47/45-A and ORF47/45-B contain a signal peptide sequence and are localized at the endoplasmic reticulum (ER). Additionally, we found that ORF47/45-A and ORF47/45-B have an extra function that mediates the upregulation of GRP78, a master regulator of ER homeostasis. The important event regarding GRP78 upregulation can be observed in all tested KSHV-positive cell lines after viral reactivation, and knockdown of GRP78 in cells significantly impairs viral lytic cycle progression, especially at late lytic stages. Compared with some other viral glycoproteins synthesized through the ER, our results strongly implicate that the ORF47/45 proteins may serve as key effectors for controlling GRP78 expression and ER homeostasis in cells. Taken together, our findings provide evidence showing the reciprocal association between the modulation of ER homeostasis and the progression of the KSHV lytic cycle.

IMPORTANCE
Emerging evidence has shown that several viruses appear to use different strategies to control ER homeostasis for supporting their productive infections. The two parts of this study identify two aspects of the association between the regulation of ER homeostasis and the progression of the KSHV lytic cycle. The first part characterizes the function of two early lytic cycle proteins, ORF47/45-A and ORF47/45-B, on the activation of a major ER chaperone protein, GRP78. In addition to the ability to promote GRP78 upregulation, the ORF47/45 proteins also activate the phosphorylation of RSK and ERK. The second part reveals that upregulation of GRP78 is essential for the progression of the KSHV lytic cycle, especially at late stages. We therefore propose that activation of GRP78 expression by viral proteins at the early lytic stage may aid with the protection of host cells from severe ER stress and may directly involve the assembly or release of virions.
Unveiling Cell Surface and Type IV Secretion Proteins Responsible for Archaeal Rudivirus Entry
Authors: Deng Ling , He Fei , Bhoobalan-Chitty Yuvaraj , Martinez-Alvarez Laura , Guo Yang , Peng Xu 
Published: June 2014

ABSTRACT

Sulfolobus
mutants resistant to archaeal lytic virus
Sulfolobus islandicus
rod-shaped virus 2 (SIRV2) were isolated, and mutations were identified in two gene clusters, cluster
sso3138
to
sso3141
and cluster
sso2386
and
sso2387
, encoding cell surface and type IV secretion proteins, respectively. The involvement of the mutations in the resistance was confirmed by genetic complementation. Blocking of virus entry into the mutants was demonstrated by the lack of early gene transcription, strongly supporting the idea of a role of the proteins in SIRV2 entry.
Acute Clearance of Human Metapneumovirus Occurs Independently of Natural Killer Cells
Authors: Wen Sherry C. , Tollefson Sharon J. , Johnson Monika , Gilchuk Pavlo , Boyd Kelli L. , Shepherd Bryan , Joyce Sebastian , Williams John V. 
Published: June 2014

ABSTRACTHuman metapneumovirus (HMPV) is a major cause of respiratory disease. The role of NK cells in protection against HMPV is unclear. We show that while HMPV-infected C57BL/6 mice had higher numbers of functional lung NK cells than mock-treated mice, comparing NK cell-depleted and control mice did not reveal differences in lung viral titers, histopathology, cytokine levels, or T cell numbers or function. These data indicate that NK cells are not required for host control of HMPV.
Characterization and Immunogenicity of a Novel Mosaic M HIV-1 gp140 Trimer
Authors: Nkolola Joseph P. , Bricault Christine A. , Cheung Ann , Shields Jennifer , Perry James , Kovacs James M. , Giorgi Elena , van Winsen Margot , Apetri Adrian , Brinkman-van der Linden Els C. M. , Chen Bing , Korber Bette , Seaman Michael S. , Barouch Dan H. 
Published: June 2014

ABSTRACT
The extraordinary diversity of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein poses a major challenge for the development of an HIV-1 vaccine. One strategy to circumvent this problem utilizes bioinformatically optimized mosaic antigens. However, mosaic Env proteins expressed as trimers have not been previously evaluated for their stability, antigenicity, and immunogenicity. Here, we report the production and characterization of a stable HIV-1 mosaic M gp140 Env trimer. The mosaic M trimer bound CD4 as well as multiple broadly neutralizing monoclonal antibodies, and biophysical characterization suggested substantial stability. The mosaic M trimer elicited higher neutralizing antibody (nAb) titers against clade B viruses than a previously described clade C (C97ZA.012) gp140 trimer in guinea pigs, whereas the clade C trimer elicited higher nAb titers than the mosaic M trimer against clade A and C viruses. A mixture of the clade C and mosaic M trimers elicited nAb responses that were comparable to the better component of the mixture for each virus tested. These data suggest that combinations of relatively small numbers of immunologically complementary Env trimers may improve nAb responses.

IMPORTANCE
The development of an HIV-1 vaccine remains a formidable challenge due to multiple circulating strains of HIV-1 worldwide. This study describes a candidate HIV-1 Env protein vaccine whose sequence has been designed by computational methods to address HIV-1 diversity. The characteristics and immunogenicity of this Env protein, both alone and mixed together with a clade C Env protein vaccine, are described.
Impaired Reduction of N
2
O to N
2
in Acid Soils Is Due to a Posttranscriptional Interference with the Expression of
nosZ
Authors: Liu Binbin , Frostegård Åsa , Bakken Lars R. 
Published: June 2014

ABSTRACT

Accumulating empirical evidence over the last 60 years has shown that the reduction of N
2
O to N
2
is impaired by low soil pH, suggesting that liming of acid soils may reduce N
2
O emissions. This option has not gained much momentum in global change research, however, possibly due to limited understanding of why low pH interferes with N
2
O reductase. We hypothesized that the reason is that denitrifying organisms in soils are unable to assemble functional N
2
O reductase (N
2
OR) at low pH, as shown to be the case for the model strain
Paracoccus denitrificans
. We tested this by experiments with bacteria extracted from soils by density gradient centrifugation. The soils were sampled from a long-term liming experiment (soil pH 4.0, 6.1, and 8.0). The cells were incubated (stirred batches, He atmosphere) at pH levels ranging from 5.7 to 7.6, while gas kinetics (NO, N
2
O, and N
2
) and abundances of relevant denitrification genes (
nirS
,
nirK
, and
nosZ
) and their transcripts were monitored. Cells from the most acidic soil (pH 4.0) were unable to reduce N
2
O at any pH. These results warrant a closer inspection of denitrification communities of very acidic soils. Cells from the neutral soils were unable to produce functional N
2
OR at pH values of ≤6.1, despite significant transcription of the
nosZ
gene. The N
2
OR expressed successfully at pH 7.0, however, was functional over the entire pH range tested (5.7 to 7.6). These observations lend strong support to our hypothesis: low soil pH diminishes/prevents reduction of N
2
O, primarily by precluding a successful assembly of functional N
2
O reductase.

IMPORTANCE
Impaired N
2
O reduction in acid soils was first observed ~60 years ago, and the phenomenon has been rediscovered several times since then. The practical implication would be that the emissions of N
2
O from cropped soils could be controlled by soil pH management, but this option has largely been ignored till now. One reason for this could be that the mechanisms involved have remained obscure. Here, we provide compelling evidence that the primary reason is that low pH interferes with the making of the enzyme N
2
O reductase rather than the function of the enzyme if properly assembled. The implications are important for understanding how pH controls the kinetics of N
2
O and N
2
production by denitrification. The improved understanding provides credibility for soil pH management as a way to mitigate N
2
O emissions.
A systematic review of the influence of occupational organophosphate pesticides exposure on neurological impairment
Authors: Takahashi Noriko , Hashizume Masahiro 
Published: June 2014

ObjectiveThe aim of this study was to conduct a systematic review of the published literature and to estimate whether or not there is a causal relationship between occupational exposure to organophosphate pesticides (OPs) and either neurological impairment or depressive symptoms.Data sourcesEMBASE, MEDLINE, Global Health and PsycINFO (1980 to April 2014).SettingObservational studies (cross-sectional, cohort and case–control studies) with exposed and unexposed groups.ParticipantsPeople who occupationally use OPs for more than 1 month and their family.Primary outcomeResults of neurological core test batteries or depressive symptoms such as headaches, anxiety and dizziness.Study appraisal and synthesis methodsAfter an extensive search of various literature databases, one author screened titles and abstracts, searched the relevant publications manually and conducted data extraction. All extracted data from the selected articles were synthesised for analysis. Quality appraisal was conducted using the Newcastle Ottawa Scale.ResultsOf the 1024 articles retrieved by database search, 24 studies that met the inclusion and exclusion criteria were selected for analysis. Of the selected studies, 17 were cross-sectional and the remaining 7 were cohort and nested case–control studies. The geographical areas included in the studies were the USA (10 studies), the UK (4 studies), Africa (4 studies), Asia (3 studies), Europe (2 studies) and South America (1 study). Each of the included studies used different exposure and outcome assessments such as neurological scores and depressive symptoms, making it difficult to compare the results exactly. Most studies showed that exposed groups had poorer results than unexposed groups; however, owing to the inconsistent neurological test batteries, there was not enough pooling evidence to conduct a meta-analysis.ConclusionsThe findings of this literature review indicate that it is necessary to standardise the neurological or neuropsychological test battery and methods of measuring exposure to OPs.
Effect of protective ventilation on postoperative pulmonary complications in patients undergoing general anaesthesia: a meta-analysis of randomised controlled trials
Authors: Tao Tianzhu , Bo Lulong , Chen Feng , Xie Qun , Zou Yun , Hu Baoji , Li Jinbao , Deng Xiaoming 
Published: June 2014

ObjectiveTo determine whether anaesthetised patients undergoing surgery could benefit from intraoperative protective ventilation strategies.MethodsMEDLINE, EMBASE and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to February 2014. Eligible studies evaluated protective ventilation versus conventional ventilation in anaesthetised patients without lung injury at the onset of mechanical ventilation. The primary outcome was the incidence of postoperative pulmonary complications. Included studies must report at least one of the following end points: the incidence of atelectasis or acute lung injury or pulmonary infections.ResultsFour studies (594 patients) were included. Meta-analysis using a random effects model showed a significant decrease in the incidence of atelectasis (OR=0.36; 95% CI 0.22 to 0.60; p<0.0001; I2=0%) and pulmonary infections (OR=0.30; 95% CI 0.14 to 0.68; p=0.004; I2=20%) in patients receiving protective ventilation. Ventilation with protective strategies did not reduce the incidence of acute lung injury (OR=0.40; 95% CI 0.07 to 2.15; p=0.28; I2=12%), all-cause mortality (OR=0.77; 95% CI 0.33 to 1.79; p=0.54; I2=0%), length of hospital stay (weighted mean difference (WMD)=−0.52 day, 95% CI −4.53 to 3.48 day; p=0.80; I2=63%) or length of intensive care unit stay (WMD=−0.55 day, 95% CI −2.19 to 1.09 day; p=0.51; I2=39%).ConclusionsIntraoperative use of protective ventilation strategies has the potential to reduce the incidence of postoperative pulmonary complications in patients undergoing general anaesthesia. Prospective, well-designed clinical trials are warranted to confirm the beneficial effects of protective ventilation strategies in surgical patients.
Triterpene glycosides from transformed root cultures of Astragalus mongholicus BGE
Authors: Tappe R. , Budzikiewicz H. , Ionkova I. , Alfermann A. W. 
Published: June 2014

Transfonned root cultures of Astragalus mongholicus Bge. have been established by infecting of sterile grown plants with AgrobacterilDfl rhizogenes strains LBA 9402 and ATCC 15834. A promoting effect of acetyl syringone on the Agrobacteriwn‐mediated hairy root (HR) initiation was obselVed. The transfonned root clones were assayed for opines by electrophoresis and 1LC. All of them were positive for agropine/mannopine. It was shown, that Astragalus‐hairy roots (HR) of the transfonned cultures produce the same kind of saponins in considerable amounts as those of intact plants. The triterpene saponins have been isolated from the methanol extract of the HR and identified as cycloartane derived saponins. On the basis of analytical data obtained by mass spectrometry (NI‐F AB‐MS, EI‐MS), and homo‐ and heteronuclear NMR experiments (DEPT, DQF‐COSY, HOHAHA, ROESY, HMQC, HMBC), the structures of three triterpenoid glycosides were determined as astragaloside I, IT, ill [1,2]. A complete assignment of the IH_ and 13C‐NMR data is given.Erratum to “Triterpene Glycosides from Transformed Root Cultures of Astragalus Mongholicus BGE”dx.doi.org/10.1155/1994/482165
A Model for the Determination of Pollen Count Using Google Search Queries for Patients Suffering from Allergic Rhinitis
Authors: König Volker , Mösges Ralph 
Published: June 2014

Background. The transregional increase in pollen-associated allergies and their diversity have been scientifically proven. However, patchy pollen count measurement in many regions is a worldwide problem with few exceptions. Methods.
This paper used data gathered from pollen count stations in Germany, Google queries using relevant allergological/biological keywords, and patient data from three German study centres collected in a prospective, double-blind, randomised, placebo-controlled, multicentre immunotherapy study to analyse a possible correlation between these data pools. Results. Overall, correlations between the patient-based, combined symptom medication score and Google data were stronger than those with the regionally measured pollen count data. The correlation of the Google data was especially strong in the groups of severe allergy sufferers. The results of the three-centre analyses show moderate to strong correlations with the Google keywords (up to >0.8 cross-correlation coefficient, P < 0.001) in 10 out of 11 groups (three averaged patient cohorts and eight subgroups of severe allergy sufferers: high IgE class, high combined symptom medication score, and asthma). Conclusion. For countries with a good Internet infrastructure but no dense network of pollen traps, this could represent an alternative for determining pollen levels and, forecasting the pollen count for the next day.
Positive Solutions for a Second-Orderp-Laplacian Boundary Value Problem with Impulsive Effects and Two Parameters
Authors: Feng Meiqiang 
Published: June 2014

The author considers an impulsive boundary value problem involving the one-dimensionalp-Laplacian-(φp (u′))′=λωtft,u,  0<t<1,  t≠tk,  Δu|t=tk=μIktk,  utk,  Δu′|t=tk=0,  k=1,2,…,n,  au(0)-bu′(0)=∫01‍g(t)u(t)dt,u′(1)=0, whereλ>0andμ>0are two parameters. Using fixed point theories, several new and more general existence and multiplicity results are derived in terms of different values ofλ>0andμ>0. The exact upper and lower bounds for these positive solutions are also given. Moreover, the approach to deal with the impulsive term is different from earlier approaches. In this paper, our results cover equations without impulsive effects and are compared with some recent results by Ding and Wang.