bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Victorivirus from a Phytopathogenic Fungus, Rosellinia necatrix, Is Infectious as Particles and Targeted by RNA Silencing
Authors: Chiba Sotaro , Lin Yu-Hsin , Kondo Hideki , Kanematsu Satoko , Suzuki Nobuhiro 
Published: April 2013

ABSTRACT

A novel victorivirus, termed
Rosellinia necatrix
victorivirus 1 (RnVV1), was isolated from a plant pathogenic ascomycete, white root rot fungus
Rosellinia necatrix
, coinfected with a partitivirus. The virus was molecularly and biologically characterized using the natural and experimental hosts (chestnut blight fungus,
Cryphonectria parasitica
). RnVV1 was shown to have typical molecular victorivirus attributes, including a monopartite double-stranded RNA genome with two open reading frames (ORFs) encoding capsid protein (CP) and RNA-dependent RNA polymerase (RdRp), a UAAUG pentamer presumed to facilitate the coupled termination/reinitiation for translation of the two ORFs, a spherical particle structure ∼40 nm in diameter, and moderate levels of CP and RdRp sequence identity (34 to 58%) to those of members of the genus
Victorivirus
within the family
Totiviridae
. A reproducible transfection system with purified RnVV1 virions was developed for the two distinct fungal hosts. Transfection assay with purified RnVV1 virions combined with virus elimination by hyphal tipping showed that the effects of RnVV1 on the phenotype of the natural host were negligible. Interestingly, comparison of the RNA silencing-competent (standard strain EP155) and -defective (Δ
dcl-2
) strains of
C. parasitica
infected with RnVV1 showed that RNA silencing acted against the virus to repress its replication, which was restored by coinfection with hypovirus or transgenic expression of an RNA silencing suppressor, hypovirus p29. Phenotypic changes were observed in the Δ
dcl-2
strain but not in EP155. This is the first reported study on the host range expansion of a
Totiviridae
member that is targeted by RNA silencing.
Vaxfectin Adjuvant Improves Antibody Responses of Juvenile Rhesus Macaques to a DNA Vaccine Encoding the Measles Virus Hemagglutinin and Fusion Proteins
Authors: Lin Wen-Hsuan W. , Vilalta Adrian , Adams Robert J. , Rolland Alain , Sullivan Sean M. , Griffin Diane E. 
Published: April 2013

ABSTRACT

DNA vaccines formulated with the cationic lipid-based adjuvant Vaxfectin induce protective immunity in macaques after intradermal (i.d.) or intramuscular (i.m.) delivery of 0.5 to 1 mg of codon-optimized DNA encoding the hemagglutinin (H) and fusion (F) proteins of measles virus (MeV). To characterize the effect of Vaxfectin at lower doses of H+F DNA, rhesus macaques were vaccinated twice with 20 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.d., 100 μg of DNA plus Vaxfectin i.m. or 100 μg of DNA plus phosphate-buffered saline (PBS) i.m. using a needleless Biojector device. The levels of neutralizing (
P
= 0.036) and binding (
P
= 0.0001) antibodies were higher after 20 or 100 μg of DNA plus Vaxfectin than after 100 μg of DNA plus PBS. Gamma interferon (IFN-γ)-producing T cells were induced more rapidly than antibody, but were not improved with Vaxfectin. At 18 months after vaccination, monkeys were challenged with wild-type MeV. None developed rash or viremia, but all showed evidence of infection. Antibody levels increased, and IFN-γ- and interleukin-17-producing T cells, including cells specific for the nucleoprotein absent from the vaccine, were induced. At 3 months after challenge, MeV RNA was detected in the leukocytes of two monkeys. The levels of antibody peaked 2 to 4 weeks after challenge and then declined in vaccinated animals reflecting low numbers of bone marrow-resident plasma cells. Therefore, Vaxfectin was dose sparing and substantially improved the antibody response to the H+F DNA vaccine. This immune response led to protection from disease (rash/viremia) but not from infection. Antibody responses after challenge were more transient in vaccinated animals than in an unvaccinated animal.
THE EUCLIDEAN DISTORTION OF FLAT TORI
Authors: HAVIV ISHAY , REGEV ODED 
Published: April 2013

We show that for every n-dimensional lattice [Formula: see text] the torus [Formula: see text] can be embedded with distortion [Formula: see text] into a Hilbert space. This improves the exponential upper bound of O(n3n/2) due to Khot and Naor (FOCS 2005, Math. Ann. 2006) and gets close to their lower bound of [Formula: see text]. We also obtain tight bounds for certain families of lattices. Our main new ingredient is an embedding that maps any point [Formula: see text] to a Gaussian function centered at u in the Hilbert space [Formula: see text]. The proofs involve Gaussian measures on lattices, the smoothing parameter of lattices and Korkine–Zolotarev bases.
Stability for a Class of Differential Equations with Nonconstant Delay
Authors: Liang Jin , Lu Tzon-Tzer , Xu Yashan 
Published: April 2013

Stability is investigated for the following differential equations with nonconstant delayx't=qtFxt-ptfxt-τt,wherep:[0,+∞)→[0,+∞),q:[0,+∞)→R,τ:[0,+∞)→[0,r], andFandf:R→Rwithxfx>0   for   x≠0   and   x≤a(ais a positive constant) are continuous functions. A criterion is given for the zero solution of this delay equation being uniformly stable and asymptotically stable.
Stem Cell Marker Nestin Is Critical for TGF-β1-Mediated Tumor Progression in Pancreatic Cancer
Authors: Su Huei-Ting , Weng Ching-Chieh , Hsiao Pi-Jung , Chen Li-Hua , Kuo Tzu-Lei , Chen Yu-Wen , Kuo Kung-Kai , Cheng Kuang-Hung 
Published: April 2013

Abstract
The stem cell marker nestin is an intermediate filament protein that plays an important role in cell integrity, migration, and differentiation. Nestin expression occurs in approximately one third of pancreatic ductal adenocarcinoma (PDAC), and its expression strongly correlates with tumor staging and metastasis. Little is known about the mechanisms by which nestin influences PDAC progression. Here, nestin overexpression in PDAC cells increased cell motility and drove phenotypic changes associated with the epithelial-mesenchymal transition (EMT) in vitro; conversely, knockdown of endogenous nestin expression reduced the migration rate and reverted cells to a more epithelial phenotype. Mouse xenograft studies showed that knockdown of nestin significantly reduced tumor incidence and volume. Nestin protein expression was associated with Smad4 status in PDAC cells; hence, nestin expression might be regulated by the TGF-β1/Smad4 pathway in PDAC. We examined nestin expression after TGF-β1 treatment in human pancreatic cancer PANC-1 and PANC-1 shSmad4 cells. The TGF-β1/Smad4 pathway induced nestin protein expression in PDAC cells in a Smad4-dependent manner. Moreover, increased nestin expression caused a positive feedback regulator of the TGF-β1 signaling system. In addition, hypoxia was shown to induce nestin expression in PDAC cells, and the hypoxia-induced expression of nestin is mediated by the TGF-β1/Smad4 pathway. Finally, the antimicrotubule inhibitors, cytochalasin D and withaferin A, exhibited anti-nestin activity; these inhibitors might be potential antimetastatic drugs. Our findings uncovered a novel role of nestin in regulating TGF-β1-induced EMT. Anti-nestin therapeutics may serve as a potential treatment for PDAC metastasis. Mol Cancer Res; 11(7); 768–79. ©2013 AACR.
Prevention of Helicobacter pylori–Induced Gastric Cancers in Gerbils by a DNA Demethylating Agent
Authors: Niwa Tohru , Toyoda Takeshi , Tsukamoto Tetsuya , Mori Akiko , Tatematsu Masae , Ushijima Toshikazu 
Published: April 2013

Abstract
Suppression of aberrant DNA methylation is a novel approach to cancer prevention, but, so far, the efficacy of the strategy has not been evaluated in cancers associated with chronic inflammation. Gastric cancers induced by Helicobacter pylori infection are known to involve aberrant DNA methylation and associated with severe chronic inflammation in their early stages. Here, we aimed to clarify whether suppression of aberrant DNA methylation can prevent H. pylori–induced gastric cancers using a Mongolian gerbil model. Administration of a DNA demethylating agent, 5-aza-2′-deoxycytidine (5-aza-dC), to gerbils (0.125 mg/kg for 50–55 weeks) decreased the incidence of gastric cancers induced by H. pylori infection and N-methyl-N-nitrosourea (MNU) treatment from 55.2% to 23.3% (P &lt; 0.05). In gastric epithelial cells, DNA methylation levels of six CpG islands (HE6, HG2, SB1, SB5, SF12, and SH6) decreased to 46% to 68% (P &lt; 0.05) of gerbils without 5-aza-dC treatment. Also, the global DNA methylation level decreased from 83.0% ± 4.5% to 80.3% ± 4.4% (mean ± SD) by 5-aza-dC treatment (P &lt; 0.05). By 5-aza-dC treatment, Il1b and Nos2 were downregulated (42% and 58% of gerbils without, respectively) but Tnf was upregulated (187%), suggesting that 5-aza-dC treatment induced dysregulation of inflammatory responses. No obvious adverse effect of 5-aza-dC treatment was observed, besides testicular atrophy. These results showed that 5-aza-dC treatment can prevent H. pylori–induced gastric cancers and suggested that removal of induced DNA methylation and/or suppression of DNA methylation induction can become a target for prevention of chronic inflammation–associated cancers. Cancer Prev Res; 6(4); 263–70. ©2013 AACR.
Pathophysiology of genetic deficiency in tissue kallikrein activity in mouse and man
Authors: Waecke Ludovic , Potier Louis , Richer Christine , Roussel Ronan , Bouby Nadine , Alhenc-Gelas Francois 
Published: April 2013

SummaryStudy of mice rendered deficient in tissue kallikrein (TK) by gene inactivation and human subjects partially deficient in TK activity as consequence of an active site mutation has allowed recognising the physiological role of TK and its peptide products kinins in arterial function and in vasodilatation, in both species. TK appears as the major kinin forming enzyme in arteries, heart and kidney. Non-kinin mediated actions of TK may occur in epithelial cells in the renal tubule. In basal condition, TK deficiency induces mild defective phenotypes in the cardiovascular system and the kidney. However, in pathological situations where TK synthesis is typically increased and kinins are produced, TK deficiency has major, deleterious consequences. This has been well documented experimentally for cardiac ischaemia, diabetes renal disease, peripheral ischaemia and aldosterone-salt induced hypertension. These conditions are all aggravated by TK deficiency. The beneficial effect of ACE/kininase II inhibitors or angiotensin II AT1 receptor antagonists in cardiac ischaemia is abolished in TK-deficient mice, suggesting a prominent role for TK and kinins in the cardioprotective action of these drugs. Based on findings made in TK-deficient mice and additional evidence obtained by pharmacological or genetic inactivation of kinin receptors, development of novel therapeutic approaches relying on kinin receptor agonism may be warranted.
The transcriptome of Leishmania majorin the axenic promastigote stage: transcript annotation and relative expression levels by RNA-seq
Authors: Rastrojo Alberto , Carrasco-Ramiro Fernando , Martín Diana , Crespillo Antonio , Reguera Rosa M , Aguado Begoña , Requena Jose M 
Published: April 2013

Abstract

Background
Although the genome sequence of the protozoan parasite Leishmania major was determined several years ago, the knowledge of its transcriptome was incomplete, both regarding the real number of genes and their primary structure.

Results
Here, we describe the first comprehensive transcriptome analysis of a parasite from the genus Leishmania. Using high-throughput RNA sequencing (RNA-seq), a total of 10285 transcripts were identified, of which 1884 were considered novel, as they did not match previously annotated genes. In addition, our data indicate that current annotations should be modified for many of the genes. The detailed analysis of the transcript processing sites revealed extensive heterogeneity in the spliced leader (SL) and polyadenylation addition sites. As a result, around 50% of the genes presented multiple transcripts differing in the length of the UTRs, sometimes in the order of hundreds of nucleotides. This transcript heterogeneity could provide an additional source for regulation as the different sizes of UTRs could modify RNA stability and/or influence the efficiency of RNA translation. In addition, for the first time for the Leishmania major promastigote stage, we are providing relative expression transcript levels.

Conclusions
This study provides a concise view of the global transcriptome of the L. major promastigote stage, providing the basis for future comparative analysis with other development stages or other Leishmania species.
Identification of microRNA-mRNA functional interactions in UVB-induced senescence of human diploid fibroblasts
Authors: Greussing Ruth , Hackl Matthias , Charoentong Pornpimol , Pauck Alexander , Monteforte Rossella , Cavinato Maria , Hofer Edith , Scheideler Marcel , Neuhaus Michael , Micutkova Lucia , Mueck Christoph , Trajanoski Zlatko , Grillari Johannes , Jansen-Dürr Pidder 
Published: April 2013

AbstractBackgroundCellular senescence can be induced by a variety of extrinsic stimuli, and sustained exposure to sunlight is a key factor in photoaging of the skin. Accordingly, irradiation of skin fibroblasts by UVB light triggers cellular senescence, which is thought to contribute to extrinsic skin aging, although molecular mechanisms are incompletely understood. Here, we addressed molecular mechanisms underlying UVB induced senescence of human diploid fibroblasts.ResultsWe observed a parallel activation of the p53/p21WAF1and p16INK4a/pRb pathways. Using genome-wide transcriptome analysis, we identified a transcriptional signature of UVB-induced senescence that was conserved in three independent strains of human diploid fibroblasts (HDF) from skin. In parallel, a comprehensive screen for microRNAs regulated during UVB-induced senescence was performed which identified five microRNAs that are significantly regulated during the process. Bioinformatic analysis of miRNA-mRNA networks was performed to identify new functional mRNA targets with high confidence for miR-15a, miR-20a, miR-20b, miR-93, and miR-101. Already known targets of these miRNAs were identified in each case, validating the approach. Several new targets were identified for all of these miRNAs, with the potential to provide new insight in the process of UVB-induced senescence at a genome-wide level. Subsequent analysis was focused on miR-101 and its putative target gene Ezh2. We confirmed that Ezh2 is regulated by miR-101 in human fibroblasts, and found that both overexpression of miR-101 and downregulation of Ezh2 independently induce senescence in the absence of UVB irradiation. However, the downregulation of miR-101 was not sufficient to block the phenotype of UVB-induced senescence, suggesting that other UVB-induced processes induce the senescence response in a pathway redundant with upregulation of miR-101.ConclusionWe performed a comprehensive screen for UVB-regulated microRNAs in human diploid fibroblasts, and identified a network of miRNA-mRNA interactions mediating UVB-induced senescence. In addition, miR-101 and Ezh2 were identified as key players in UVB-induced senescence of HDF.
Consumers’ intention to use health recommendation systems to receive personalized nutrition advice
Authors: Wendel Sonja , Dellaert Benedict GC , Ronteltap Amber , van Trijp Hans CM 
Published: April 2013

Abstract

Background
Sophisticated recommendation systems are used more and more in the health sector to assist consumers in healthy decision making. In this study we investigate consumers' evaluation of hypothetical health recommendation systems that provide personalized nutrition advice. We examine consumers' intention to use such a health recommendation system as a function of options related to the underlying system (e.g. the type of company that generates the advice) as well as intermediaries (e.g. general practitioner) that might assist in using the system. We further explore if the effect of both the system and intermediaries on intention to use a health recommendation system are mediated by consumers' perceived effort, privacy risk, usefulness and enjoyment.

Methods
204 respondents from a consumer panel in the Netherlands participated. The data were collected by means of a questionnaire. Each respondent evaluated three hypothetical health recommendation systems on validated multi-scale measures of effort, privacy risk, usefulness, enjoyment and intention to use the system. To test the hypothesized relationships we used regression analyses.

Results
We find evidence that the options related to the underlying system as well as the intermediaries involved influence consumers' intention to use such a health recommendation system and that these effects are mediated by perceptions of effort, privacy risk, usefulness and enjoyment. Also, we find that consumers value usefulness of a system more and enjoyment less when a general practitioner advices them to use a health recommendation system than if they use it out of their own curiosity.

Conclusions
We developed and tested a model of consumers' intention to use a health recommendation system. We found that intermediaries play an important role in how consumers evaluate such a system over and above options of the underlying system that is used to generate the recommendation. Also, health-related information services seem to rely on endorsement by the medical sector. This has considerable implications for the distribution as well as the communication channels of health recommendation systems which may be quite difficult to put into practice outside traditional health service channels.
1H-NMR based metabonomic profiling of human esophageal cancer tissue
Authors: Wang Liang , Chen Jie , Chen Longqi , Deng Pengchi , bu Qian , Xiang Pu , Li Manli , Lu Wenjie , Xu Youzhi , Lin Hongjun , Wu Tianming , Wang Huijuan , Hu Jing , Shao Xiaoni , Cen Xiaobo , Zhao Ying-Lan 
Published: April 2013

Abstract

Background
The biomarker identification of human esophageal cancer is critical for its early diagnosis and therapeutic approaches that will significantly improve patient survival. Specially, those that involves in progression of disease would be helpful to mechanism research.

Methods
In the present study, we investigated the distinguishing metabolites in human esophageal cancer tissues (n = 89) and normal esophageal mucosae (n = 26) using a 1H nuclear magnetic resonance (1H-NMR) based assay, which is a highly sensitive and non-destructive method for biomarker identification in biological systems. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least-squares-discriminant anlaysis (OPLS-DA) were applied to analyse 1H-NMR profiling data to identify potential biomarkers.

Results
The constructed OPLS-DA model achieved an excellent separation of the esophageal cancer tissues and normal mucosae. Excellent separation was obtained between the different stages of esophageal cancer tissues (stage II = 28; stage III = 45 and stage IV = 16) and normal mucosae. A total of 45 metabolites were identified, and 12 of them were closely correlated with the stage of esophageal cancer. The downregulation of glucose, AMP and NAD, upregulation of formate indicated the large energy requirement due to accelerated cell proliferation in esophageal cancer. The increases in acetate, short-chain fatty acid and GABA in esophageal cancer tissue revealed the activation of fatty acids metabolism, which could satisfy the need for cellular membrane formation. Other modified metabolites were involved in choline metabolic pathway, including creatinine, creatine, DMG, DMA and TMA. These 12 metabolites, which are involved in energy, fatty acids and choline metabolism, may be associated with the progression of human esophageal cancer.

Conclusion
Our findings firstly identify the distinguishing metabolites in different stages of esophageal cancer tissues, indicating the attribution of metabolites disturbance to the progression of esophageal cancer. The potential biomarkers provide a promising molecular diagnostic approach for clinical diagnosis of human esophageal cancer and a new direction for the mechanism study.
Engineering of papaya mosaic virus (PapMV) nanoparticles with a CTL epitope derived from influenza NP
Authors: Babin Cindy , Majeau Nathalie , Leclerc Denis 
Published: April 2013

Abstract

Background
The ever-present threat of infectious disease, e.g. influenza pandemics, and the increasing need for new and effective treatments in immunotherapy are the driving forces that motivate research into new and innovative vaccine platforms. Ideally, such platforms should trigger an efficient CTL response, be safe, and easy to manufacture. We recently developed a novel nanoparticle adjuvant comprised of papaya mosaic virus (PapMV) coat protein (CP) assembled around an RNA. The PapMV nanoparticle is an efficient vaccine platform in which the peptide antigen is fused to the C-terminus of the PapMV CP, leading to nanoparticles presenting surface-exposed epitope. The fusion stabilizes the epitope and improves its immunogenicity. We found recently that C-terminal fusions are not always efficient, depending on the nature of the peptide fused to the platform.

Results
We chose a CTL epitope derived from the nucleocapsid (NP) of influenza virus (NP147-155) for this proof-of-concept demonstration. Recombinant nanoparticles harbouring a fusion at the N-terminus were more efficient in triggering a CTL response. Efficacy appeared to be linked to the stability of the nanoparticles at 37°C. We also showed that discs—smaller than nanoparticles—made of 20 subunits of PapMV CP are less efficient for induction of a CTL response in mice, revealing that assembly of the recombinant PapMV CP into nanoparticles is crucial to triggering an efficient CTL response.

Conclusion
The point of fusion on the PapMV vaccine platform is critical to triggering an efficient CTL response. Efficacy is linked to nanoparticle stability; nanoparticles must be stable at 37°C but remain susceptible to cellular proteases to ensure efficient processing of the CTL epitope by cells of the immune system. The results of this study improve our understanding of the PapMV vaccine platform, which will facilitate the design of efficient vaccines to various infectious threats.