bluuebunny/crossref_metadata_2025 huggingface dataset:
Influenza A Virus Hemagglutinin and Neuraminidase Mutually Accelerate Their Apical Targeting through Clustering of Lipid Rafts
Authors: Ohkura Takashi , Momose Fumitaka , Ichikawa Reiko , Takeuchi Kaoru , Morikawa Yuko
Published: June 2014

In polarized epithelial cells, influenza A virus hemagglutinin (HA) and neuraminidase (NA) are intrinsically associated with lipid rafts and target the apical plasma membrane for viral assembly and budding. Previous studies have indicated that the transmembrane domain (TMD) and cytoplasmic tail (CT) of HA and NA are required for association with lipid rafts, but the raft dependencies of their apical targeting are controversial. Here, we show that coexpression of HA with NA accelerated their apical targeting through accumulation in lipid rafts. HA was targeted to the apical plasma membrane even when expressed alone, but the kinetics was much slower than that of HA in infected cells. Coexpression experiments revealed that apical targeting of HA and NA was accelerated by their coexpression. The apical targeting of HA was also accelerated by coexpression with M1 but not M2. The mutations in the outer leaflet of the TMD and the deletion of the CT in HA and NA that reduced their association with lipid rafts abolished the acceleration of their apical transport, indicating that the lipid raft association is essential for efficient apical trafficking of HA and NA. An
in situ
proximity ligation assay (PLA) revealed that HA and NA were accumulated and clustered in the cytoplasmic compartments only when both were associated with lipid rafts. Analysis with mutant viruses containing nonraft HA/NA confirmed these findings. We further analyzed lipid raft markers by
in situ
PLA and suggest a possible mechanism of the accelerated apical transport of HA and NA via clustering of lipid rafts.

IMPORTANCE
Lipid rafts serve as sites for viral entry, particle assembly, and budding, leading to efficient viral replication. The influenza A virus utilizes lipid rafts for apical plasma membrane targeting and particle budding. The hemagglutinin (HA) and neuraminidase (NA) of influenza virus, key players for particle assembly, contain determinants for apical sorting and lipid raft association. However, it remains to be elucidated how lipid rafts contribute to the apical trafficking and budding. We investigated the relation of lipid raft association of HA and NA to the efficiency of apical trafficking. We show that coexpression of HA and NA induces their accumulation in lipid rafts and accelerates their apical targeting, and we suggest that the accelerated apical transport likely occurs by clustering of lipid rafts at the TGN. This finding provides the first evidence that two different raft-associated viral proteins induce lipid raft clustering, thereby accelerating apical trafficking of the viral proteins.
Changes in Protein Domains outside the Catalytic Site of the Bacteriophage Qβ Replicase Reduce the Mutagenic Effect of 5-Azacytidine
Authors: Cabanillas Laura , Sanjuán Rafael , Lázaro Ester
Published: June 2014

The high genetic heterogeneity and great adaptability of RNA viruses are ultimately caused by the low replication fidelity of their polymerases. However, single amino acid substitutions that modify replication fidelity can evolve in response to mutagenic treatments with nucleoside analogues. Here, we investigated how two independent mutants of the bacteriophage Qβ replicase (Thr210Ala and Tyr410His) reduce sensitivity to the nucleoside analogue 5-azacytidine (AZC). Despite being located outside the catalytic site, both mutants reduced the mutation frequency in the presence of the drug. However, they did not modify the type of AZC-induced substitutions, which was mediated mainly by ambiguous base pairing of the analogue with purines. Furthermore, the Thr210Ala and Tyr410His substitutions had little or no effect on replication fidelity in untreated viruses. Also, both substitutions were costly in the absence of AZC or when the action of the drug was suppressed by adding an excess of natural pyrimidines (uridine or cytosine). Overall, the phenotypic properties of these two mutants were highly convergent, despite the mutations being located in different domains of the Qβ replicase. This suggests that treatment with a given nucleoside analogue tends to select for a unique functional response in the viral replicase.

IMPORTANCE
In the last years, artificial increase of the replication error rate has been proposed as an antiviral therapy. In this study, we investigated the mechanisms by which two substitutions in the Qβ replicase confer partial resistance to the mutagenic nucleoside analogue AZC. As opposed to previous work with animal viruses, where different mutations selected sequentially conferred nucleoside analogue resistance through different mechanisms, our results suggest that there are few or no alternative AZC resistance phenotypes in Qβ. Also, despite resistance mutations being highly costly in the absence of the drug, there was no sequential fixation of secondary mutations. Bacteriophage Qβ is the virus with the highest reported mutation rate, which should make it particularly sensitive to nucleoside analogue treatments, probably favoring resistance mutations even if they incur high costs. The results are also relevant for understanding the possible pathways by which fidelity of the replication machinery can be modified.
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

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

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

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

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

Human 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

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

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.
Clinically relevant interaction between warfarin and scuppernongs, a quercetin containing muscadine grape: continued questions surrounding flavonoid-induced warfarin interactions
Authors: Woodward Christopher J , Deyo Zachariah M , Donahue Katrina E , Deal Allison M , Hawes Emily M
Published: June 2014

We present a case of clinically relevant and probable interaction between warfarin and scuppernongs in a 73-year-old woman where ingestion of scuppernongs, a variety of quercetin-containing muscadine grapes, over a period of 2 months was associated with elevations in the International Normalised Ratio to supratherapeutic levels. While muscadine grapes and specifically scuppernongs are found primarily in Southeastern USA, the flavonoid in questionand quercetin is found worldwide as a dietary supplement.
Torsion of an intraperitoneal undescended seminomatous testicular tumour
Authors: McDermott Frank Denis , Heeney Anna , Kelly Michael E , Winter Des C
Published: June 2014

A 42-year-old man presented acutely with lower abdominal peritonism and a medical history of a right orchidopexy as a child. Further history from his mother revealed that during the procedure the left testicle could not be found. In view of his unusual history and the nature of the pain a CT scan was performed demonstrating a 10×8 cm solid mass above the bladder. The mass was removed electively and revealed a torted left testicular mass. Histopathology confirmed a torted seminomatous tumour. This case highlights the importance of returning undescended testes to the scrotum or confirming absence to preserve function and ease surveillance of potential future neoplastic transformation. The current management for impalpable undescended/absent testicles involves radiological imaging, inguinal and/or laparoscopic exploration and orchidopexy before 18 months of age.
Bilateral adrenal haemorrhage leading to adrenal crisis
Authors: McGowan-Smyth Sam
Published: June 2014

A 77-year-old man presented with an acute worsening of chronic back pain. CT showed dense bilateral adrenal glands suggestive of adrenalhaemorrhagewhich was confirmed by MRI. Despite appropriate glucocorticoid replacement for adrenal insufficiency, 7 days after admission this patient suffered an adrenal crisis. Owing to the timely diagnosis, appropriate treatment was given and the patient survived. Large bilateral adrenal haemorrhage however, can lead to cardiovascular collapse and death if not appropriately diagnosed and managed promptly. Despite its rarity, bilateral adrenal haemorrhage should always be considered as a differential for back pain in the setting of an acute illness due to its potentially fatal consequences.
A systematic review of the influence of occupational organophosphate pesticides exposure on neurological impairment
Authors: Takahashi Noriko , Hashizume Masahiro
Published: June 2014

Objective

The 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 sources

EMBASE, MEDLINE, Global Health and PsycINFO (1980 to April 2014).

Setting

Observational studies (cross-sectional, cohort and case–control studies) with exposed and unexposed groups.

Participants

People who occupationally use OPs for more than 1 month and their family.

Primary outcome

Results of neurological core test batteries or depressive symptoms such as headaches, anxiety and dizziness.

Study appraisal and synthesis methods

After 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.

Results

Of 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.

Conclusions

The 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

Objective

To determine whether anaesthetised patients undergoing surgery could benefit from intraoperative protective ventilation strategies.

Methods

MEDLINE, 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.

Results

Four 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%).

Conclusions

Intraoperative 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.
One health, many histories
Authors: Woods Abigail , Bresalier Michael
Published: June 2014

In another of Veterinary Record 's series of articles on One Health, Abigail Woods and Michael Bresalier discuss the complex history of veterinary‐medical collaboration and highlight the social, political and institutional factors that have contributed towards shaping the One Health model
Involvement of ERK1/2, p38 MAPK, and PI3K/Akt signaling pathways in the regulation of cell cycle progression by PTHrP in colon adenocarcinoma cells
Authors: Calvo Natalia , Martín María Julia , de Boland Ana Russo , Gentili Claudia
Published: June 2014

Parathyroid hormone-related peptide (PTHrP) is distributed in most fetal and adult tissues, and its expression correlates with the severity of colon carcinoma. Recently we obtained evidence that in Caco-2 cells, a cell line from human colorectal adenocarcinoma, exogenous PTHrP increases the number of live cells, via ERK1/2, p38 MAPK, and PI3-kinase and induces the expression of cyclin D1, a cell cycle regulatory protein. In this study, we further investigated the role of PTHrP in the regulation of the cell cycle progression in these intestinal cells. Flow cytometry analysis revealed that PTHrP treatment diminishes the number of cells in the G0/G1 phase and increases the number in both S and G2/M phases. The hormone increases the expression of CDK6 and diminishes the amount of negative cell cycle regulators p27Kip1, p15INK4B, and p53. However, PTHrP does not modify the expression of cyclin D3, CDK4, and p16INK4A. In addition, inhibitors of ERK1/2 (PD98059), p38 MAPK (SB203580), and PI3Kinase (LY294002) reversed PTHrP response in Caco-2 cells. Taken together, our results suggest that PTHrP positively modulates cell cycle progression and changes the expression of proteins involved in cell cycle regulation via ERK1/2, p38 MAPK, and PI3K signaling pathways in Caco-2 cells.
Leaf secretory tissues in Myrsine coriacea and Myrsine venosa (Primulaceae): ontogeny, morphology, and chemical composition of essential oils
Authors: de Luna Bruna Nunes , Defaveri Anna Carina Antunes e , Sato Alice , Bizzo Humberto Ribeiro , Freitas Maria de Fátima , Barros Claudia Franca
Published: June 2014

Secretory structures are an outstanding feature in Primulaceae (Ericales). Such structures are known for their taxonomical and medicinal importance. However, a detailed morphological study of the secretory structures in Primulaceae has been neglected. Selected species for this study belong to Myrsine, a widely distributed genus in Brazil, popularly known as “capororoca”. In this study, we aimed to elucidate the ontogenesis of the secretory structures in the leaves of Myrsine coriacea (Sw.) R. Br. ex Roem & Schult. and Myrsine venosa A.DC. and report, for the first time, on the composition of their essential oils. The following secretory structures are found in M. coriacea and M. venosa: idioblasts, glandular trichomes, and secretory cavities. The development of all secretory structures, which is asynchronous, occurs during leaf expansion and differentiation; therefore, in leaf primordia, the same type of secretory structure could be observed at different stages of differentiation. By the complete expansion of leaf primordia, all secretory structures have reached their full size. Idioblasts are derived from both protodermal and ground meristem cells and they secrete mucilage or phenolic compounds. The glandular trichomes can be peltate, as found in both species, or branched, as found only in M. coriacea. Trichomes are initiated by the enlargement of protodermal cells, followed by their division, and they are completely formed by the end of leaf expansion. Secretory cavities are schizogenous and originated from ground meristem cells. Major components from M. coriacea essential oils were β-elemene, γ-muurolene, and α-cadinene, while the major components of M. venosa essential oils were β-caryophyllene, γ-muurolene, and δ-cadinene.
Stochastic bifurcation in a model of love with colored noise
Authors: Yue Xiaokui , Dai Honghua , Yuan Jianping
Published: June 2014

In this paper, we wish to examine the stochastic bifurcation induced by multiplicative Gaussian colored noise in a dynamical model of love where the random factor is used to describe the complexity and unpredictability of psychological systems. First, the dynamics in deterministic love-triangle model are considered briefly including equilibrium points and their stability, chaotic behaviors and chaotic attractors. Then, the influences of Gaussian colored noise with different parameters are explored such as the phase plots, top Lyapunov exponents, stationary probability density function (PDF) and stochastic bifurcation. The stochastic P-bifurcation through a qualitative change of the stationary PDF will be observed and bifurcation diagram on parameter plane of correlation time and noise intensity is presented to find the bifurcation behaviors in detail. Finally, the top Lyapunov exponent is computed to determine the D-bifurcation when the noise intensity achieves to a critical value. By comparison, we find there is no connection between two kinds of stochastic bifurcation.
A note on entropy relations of black hole horizons
Authors: Meng Xin-He , Xu Wei , Wang Jia
Published: June 2014

Black holes with multi-horizons may provide new ways to understand the intrinsic thermodynamics. In this work, we focus on the entropy relations of black holes in three, four and higher dimensions. These entropy relations include entropy product, "part" entropy product and entropy sum. We also discuss their differences and similarities, in order to make a further study on understanding the origin of black hole entropy at the microscopic level.
Low temperature photoluminescence and deformation luminescence of microparticles SrAl2O4:(Eu2+, Dy3+) in a matrix of photopolymer
Authors: Banishev A. A. , Lotin A. A. , Banishev A. F.
Published: June 2014

The paper deals with low-temperature photoluminescence and deformation luminescence (mechanoluminescence) of a composite material based on fine disperse powder of phosphor SrAl 2 O 4:( Eu 2+, Dy 3+) and photopolymerizing resin that is transparent in the visible region. New information about the energy levels of impurities and defects was obtained. It has been found that at low temperatures (T = 15 ÷ 200 K) the photoluminescence spectrum of SrAl 2 O 4:( Eu 2+, Dy 3+) presents two partially overlapping wide bands with the maxima at λ1 max = 446 nm and λ2 max = 517 nm. The strong interaction of energy states of the bands results in temperature quenching of the short-wave band of luminescence (λ1 max = 446 nm) and its complete attenuation at T ≥ 200 K. The results were used to describe the mechanism of persistent luminescence and mechanoluminescence of SrAl 2 O 4:( Eu 2+, Dy 3+).
Annealing study of amorphous bulk and nanoparticle iron using molecular dynamics simulation
Authors: Kien P. H. , Lan M. T. , Dung N. T. , Hung P. K.
Published: June 2014

Annealing study of amorphous bulk and nanoparticle iron at temperatures from 500 K to 1000 K has been carried out using molecular dynamics (MD) simulations. The simulation is performed for models containing 104 particles Fe at both crystalline and amorphous states. We determine changes of the potential energy, pair radial distribution function (PRDF) and distribution of coordination number (DCN) as a function of annealing time. The calculation shows that the aging slightly reduces the potential energy of system. This result evidences that the amorphous sample undergoes different quasi-equilibrated states during annealing. Similar trend is observed for nanoparticles sample. When the samples are annealed at high temperatures we observe the crystallization in both bulk and nanoparticle. In particular, the system undergoes three stages. At first stage the relaxation proceeds slowly so that the energy of system slightly decreases and the samples structure remains amorphous. Within second stage a structural transformation occurs which significantly changes PRDF and DCN for the relatively short time. The energy of the system is dropped considerably and the amorphous structure transforms into the crystalline. Finally, the crystalline sample undergoes the slow relaxation which reduces the energy of system and eliminates structural defects in crystal lattices.
Invariants of virtual rational moves
Authors: Khan Noureen A.
Published: June 2014

Generalized Reidemeister moves provide an extended set of moves to work with virtual knots and links. We introduce virtual tangle moves, generalization of classical rational tangle moves and show that such generalizations are essential to develop new invariants of virtual knots and links. We show that every 2-algebraic virtual link is a virtual 4-move equivalent to a trivial link or Hopf link. The properties of virtual tangle move are analyzed on few existing invariants associated with virtual knots and links.
EFFICIENT COMPUTATION OF EXPOSURE PROFILES FOR COUNTERPARTY CREDIT RISK
Authors: DE GRAAF CORNELIS S. L. , FENG QIAN , KANDHAI DRONA , OOSTERLEE CORNELIS W.
Published: June 2014

Three computational techniques for approximation of counterparty exposure for financial derivatives are presented. The exposure can be used to quantify so-called Credit Valuation Adjustment (CVA) and Potential Future Exposure (PFE), which are of utmost importance for modern risk management in the financial industry, especially since the recent credit crisis. The three techniques all involve a Monte Carlo path discretization and simulation of the underlying entities. Along the generated paths, the corresponding values and distributions are computed during the entire lifetime of the option. Option values are computed by either the finite difference method for the corresponding partial differential equations, or the simulation-based Stochastic Grid Bundling Method (SGBM), or by the COS method, based on Fourier-cosine expansions. In this research, numerical results are presented for early-exercise options. The underlying asset dynamics are given by either the Black–Scholes or the Heston stochastic volatility model.
CLOSED-FORM APPROXIMATION OF PERPETUAL TIMER OPTION PRICES
Authors: LI MINQIANG , MERCURIO FABIO
Published: June 2014

We develop an asymptotic expansion technique for pricing timer options in stochastic volatility models when the effect of volatility of variance is small. Based on the pricing PDE, closed-form approximation formulas have been obtained. The approximation has an easy-to-understand Black–Scholes-like form and many other attractive properties. Numerical analysis shows that the approximation formulas are very fast and accurate, especially when the volatility of variance is not large.
The connections of pseudo-Finsler spaces
Authors: Minguzzi E.
Published: June 2014

We give an introduction to (pseudo-)Finsler geometry and its connections. For most results we provide short and self-contained proofs. Our study of the Berwald nonlinear connection is framed into the theory of connections over general fibered spaces pioneered by Mangiarotti, Modugno and other scholars. The main identities for the linear Finsler connection are presented in the general case, and then specialized to some notable cases like Berwald's, Cartan's or Chern–Rund's. In this way it becomes easy to compare them and see the advantages of one connection over the other. Since we introduce two soldering forms we are able to characterize the notable Finsler connections in terms of their torsion properties. As an application, the curvature symmetries implied by the compatibility with a metric suggest that in Finslerian generalizations of general relativity the mean Cartan torsion vanishes. This observation allows us to obtain dynamical equations which imply a satisfactory conservation law. The work ends with a discussion of yet another Finsler connection which has some advantages over Cartan's and Chern–Rund's.
FREE VIBRATION OF FUNCTIONALLY GRADED THIN RECTANGULAR PLATES RESTING ON WINKLER ELASTIC FOUNDATION WITH GENERAL BOUNDARY CONDITIONS USING RAYLEIGH–RITZ METHOD
Authors: CHAKRAVERTY S. , PRADHAN K. K.
Published: June 2014

In this paper, free vibration of functionally graded (FG) rectangular plates subject to different sets of boundary conditions within the framework of classical plate theory is investigated. Rayleigh–Ritz method is used to obtain the generalized eigenvalue problem. Trial functions denoting the displacement components are expressed in simple algebraic polynomial forms which can handle any sets of boundary conditions. Material properties of the FG plate are assumed to vary continuously in the thickness direction of the constituents according to power-law form. The objective is to study the effects of constituent volume fractions, aspect ratios and power-law indices on the natural frequencies. New results for frequency parameters are incorporated after performing a test of convergence. Comparison with the results from the existing literature are provided for validation in special cases. Three-dimensional mode shapes are presented for FG square plates having various boundary conditions at the edges for different power-law indices. The present investigation also involves the rectangular FG plate to lay on a uniform Winkler elastic foundation. New results for the eigenfrequencies associated with foundation parameters are also reported here with the validation in special cases after checking a convergence pattern.
FACILE SOLVOTHERMAL SYNTHESIS OF MESOSTRUCTURED CHITOSAN-COATED Fe3O4 NANOPARTICLES AND ITS FURTHER MODIFICATION WITH FOLIC ACID FOR IMPROVING TARGETED DRUG DELIVERY
Authors: SHEN MAO , WU CHENGLIN , LIN CAIPING , FAN GUODONG , JIN YANGMIN , ZHANG ZHILI , LI CHENGHONG , JIA WENPING
Published: June 2014

Mesostructured chitosan-coated Fe 3 O 4 nanoparticles (CS-coated Fe 3 O 4 NPs) were synthesized by a facile one-step solvothermal method via using chitosan as a surface-modification agent. Subsequently, the surfaces of CS-coated Fe 3 O 4 NPs were successfully conjugated with folic acid (FA) molecules to obtain FA–CS-coated Fe 3 O 4 NPs for improving targeted drug delivery. The morphology, chemical component and magnetic property of as-prepared composite nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), dynamic light scattering (DLS), scanning transmission electron microscopy (SEM), transmission electron microscopy (TEM), thermal gravimetric analysis (TGA) and vibrating sample magnetometer (VSM). Furthermore, doxorubicin hydrochloride (DOX) as a model drug was encapsulated for investigating drug release pattern in vitro. The results show that the magnetization saturation value of FA–CS-coated Fe 3 O 4 NPs was about 28.5 emu/g, exhibiting superparamagnetic properties and mesostructure. DOX could be loaded to FA–CS-coated Fe 3 O 4 NPs with high capacity about 27.9%, and the release rate of DOX could be adjusted by the pH value. This work demonstrates that the prepared magnetic nanoparticles have potential applications in the treatment of cancer as targeting drug delivery carriers.
SYNTHESIS AND FLUORESCENCE PROPERTIES OF LaF3:Tb3+ PHOSPHORS VIA ULTRASONIC-ASSISTED IONIC LIQUID METHOD
Authors: ZHU LING , LIU SANXI , HUI YU , ZOU BINGLIN , CAO XUEQIANG
Published: June 2014

Hexagonal phase LaF 3: Tb 3+ nano/microcrystals were successfully synthesized via ultrasonic-assisted ionic liquid (IL) method. The field emission scanning electron microscope (FESEM) images revealed that the morphologies of the as-prepared LaF 3: Tb 3+ samples were gradually converted from nanoplates to microcylinders with increasing the concentration of Tb 3+ ions. The photoluminescent (PL) spectrum shows that all the as-prepared La 1-x Tb x F 3 samples show the characteristic emissions of Tb 3+5 D 4 → 7 F J (J = 6-3, with 5 D 4 → 7 F 5 green emission at 542 nm as the strongest one) transitions. The optimal Tb 3+-doped concentration is 20 mol.% in the LaF 3 host. The photoluminescence intensity of the La 0.80 Tb 0.20 F 3 microcylinders prepared by ultrasonic irradiation was largely improved as compared with that of the product prepared by stirring.
Hall effects on peristaltic flow of couple stress fluid in an inclined asymmetric channel
Authors: Hayat T. , Iqbal Maryam , Yasmin Humaira , Alsaadi Fuad
Published: June 2014

Effect of Hall current on peristaltic transport of couple stress fluid in an inclined asymmetric channel is investigated. An incompressible fluid is conducting in the presence of inclined magnetic field. Problem formulation is developed through heat and mass transfer aspects. Soret and Dufour effects are present. Long wavelength and low Reynolds number approaches are adopted. Closed form expression for longitudinal velocity, pressure gradient, temperature and concentration are presented. Important results reflecting the influence of embedded parameters in the problems have been pointed out. Pumping and trapping phenomena are especially focused.
Evidence from mathematical modeling that carbonic anhydrase II and IV enhance CO2 fluxes across Xenopus oocyte plasma membranes
Authors: Occhipinti Rossana , Musa-Aziz Raif , Boron Walter F.
Published: June 2014

Exposing an oocyte to CO2/HCO3− causes intracellular pH (pHi) to decline and extracellular-surface pH (pHS) to rise to a peak and decay. The two companion papers showed that oocytes injected with cytosolic carbonic anhydrase II (CA II) or expressing surface CA IV exhibit increased maximal rate of pHi change (dpHi/d t)max, increased maximal pHS changes (ΔpHS), and decreased time constants for pHi decline and pHS decay. Here we investigate these results using refinements of an earlier mathematical model of CO2 influx into a spherical cell. Refinements include 1) reduced cytosolic water content, 2) reduced cytosolic diffusion constants, 3) refined CA II activity, 4) layer of intracellular vesicles, 5) reduced membrane CO2 permeability, 6) microvilli, 7) refined CA IV activity, 8) a vitelline membrane, and 9) a new simulation protocol for delivering and removing the bulk extracellular CO2/HCO3− solution. We show how these features affect the simulated pHi and pHS transients and use the refined model with the experimental data for 1.5% CO2/10 mM HCO3− (pHo = 7.5) to find parameter values that approximate ΔpHS, the time to peak pHS, the time delay to the start of the pHi change, (dpHi/d t)max, and the change in steady-state pHi. We validate the revised model against data collected as we vary levels of CO2/HCO3− or of extracellular HEPES buffer. The model confirms the hypothesis that CA II and CA IV enhance transmembrane CO2 fluxes by maximizing CO2 gradients across the plasma membrane, and it predicts that the pH effects of simultaneously implementing intracellular and extracellular-surface CA are supra-additive.
Calcium sensitivity of residual force enhancement in rabbit skinned fibers
Authors: Joumaa V. , Herzog W.
Published: June 2014

Isometric force after active stretch of muscles is higher than the purely isometric force at the corresponding length. This property is termed residual force enhancement. Active force in skeletal muscle depends on calcium attachment characteristics to the regulatory proteins. Passive force has been shown to influence calcium attachment characteristics, specifically the sarcomere length dependence of calcium sensitivity. Since one of the mechanisms proposed to explain residual force enhancement is the increase in passive force that results from engagement of titin upon activation and stretch, our aim was to test if calcium sensitivity of residual force enhancement was different from that of its corresponding purely isometric contraction and if such a difference was related to the molecular spring titin. Force-pCa curves were established in rabbit psoas skinned fibers for reference and residual force-enhanced states at a sarcomere length of 3.0 μm 1) in a titin-intact condition, 2) after treatment with trypsin to partially eliminate titin, and 3) after treatment with trypsin and osmotic compression with dextran T-500 to decrease the lattice spacing in the absence of titin. The force-pCa curves of residual force enhancement were shifted to the left compared with their corresponding controls in titin-intact fibers, indicating increased calcium sensitivity. No difference in calcium sensitivity was observed between reference and residual force-enhanced contractions in trypsin-treated and osmotically compressed trypsin-treated fibers. Furthermore, calcium sensitivity after osmotic compression was lower than that observed for residual force enhancement in titin-intact skinned fibers. These results suggest that titin-based passive force regulates the increase in calcium sensitivity of residual force enhancement by a mechanism other than reduction of the myofilament lattice spacing.