bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between hexon and L4-100K determines virus rescue and growth of hexon-chimeric recombinant Ad5 vectors
Authors: Yan Jingyi , Dong Jianing , Wu Jiaxin , Zhu Rui , Wang Zhen , Wang Baoming , Wang Lizheng , Wang Zixuan , Zhang Haihong , Wu Hui , Yu Bin , Kong Wei , Yu Xianghui 
Published: March 2016

AbstractThe immunogenicity of recombinant adenovirus serotype 5 (rAd5) vectors has been shown to be suppressed by neutralizing antibodies (NAbs) directed primarily against hexon hypervariable regions (HVRs). Preexisting immunity can be circumvented by replacing HVRs of rAd5 hexon with those derived from alternate adenovirus serotypes. However, chimeric modification of rAd5 hexon HVRs tends to cause low packaging efficiency or low proliferation of rAd5 vectors, but the related mechanism remains unclear. In this study, several Ad5-based vectors with precise replacement of HVRs with those derived from Ad37 and Ad43 were generated. We first observed that a HVR-exchanged rAd5 vector displayed a higher efficacy of the recombinant virus rescue and growth improvement compared with the rAd5 vector, although most hexon-chimeric rAd5 vectors constructed by us and other groups have proven to be nonviable or growth defective. We therefore evaluated the structural stability of the chimeric hexons and their interactions with the L4-100K chaperone. We showed that the viability of hexon-chimeric Ad5 vectors was not attributed to the structural stability of the chimeric hexon, but rather to the hexon maturation which was assisted by L4-100K. Our results suggested that the intricate interaction between hexon and L4-100K would determine the virus rescue and proliferation efficiency of hexon-chimeric rAd5 vectors.
Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations
Authors: Goldar A. , Arneodo A. , Audit B. , Argoul F. , Rappailles A. , Guilbaud G. , Petryk N. , Kahli M. , Hyrien O. 
Published: March 2016

AbstractWe propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations and by taking into account the chromatin’s fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.
Six Susceptible-Infected-Susceptible Models on Scale-free Networks
Authors: Morita Satoru 
Published: March 2016

AbstractSpreading phenomena are ubiquitous in nature and society. For example, disease and information spread over underlying social and information networks. It is well known that there is no threshold for spreading models on scale-free networks; this suggests that spread can occur on such networks, regardless of how low the contact rate may be. In this paper, I consider six models with different contact and propagation mechanisms, which include models studied so far, but are apt to be confused. To compare these six models, I analyze them by degree-based mean-field theory. I find that the result depends on the details of contact and propagation mechanism.
Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia
Authors: Duval Céline Z. , Goumon Yannick , Kemmel Véronique , Kornmeier Jürgen , Dufour André , Andlauer Olivier , Vidailhet Pierre , Poisbeau Pierrick , Salvat Eric , Muller André , Mensah-Nyagan Ayikoé G. , Schmidt-Mutter Catherine , Giersch Anne 
Published: March 2016

AbstractPatients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients’ evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers.
The Prevalence and Distribution of Neurodegenerative Compound-Producing Soil Streptomyces spp.
Authors: Watkins Anna L. , Ray Arpita , R. Roberts Lindsay , Caldwell Kim A. , Olson Julie B. 
Published: March 2016

AbstractRecent work from our labs demonstrated that a metabolite(s) from the soil bacterium Streptomyces venezuelae caused dopaminergic neurodegeneration in Caenorhabditis elegans and human neuroblastoma cells. To evaluate the capacity for metabolite production by naturally occurring streptomycetes in Alabama soils, Streptomyces were isolated from soils under different land uses (agriculture, undeveloped, and urban). More isolates were obtained from agricultural than undeveloped soils; there was no significant difference in the number of isolates from urban soils. The genomic diversity of the isolates was extremely high, with only 112 of the 1509 isolates considered clones. A subset was examined for dopaminergic neurodegeneration in the previously established C. elegans model; 28.3% of the tested Streptomyces spp. caused dopaminergic neurons to degenerate. Notably, the Streptomyces spp. isolates from agricultural soils showed more individual neuron damage than isolates from undeveloped or urban soils. These results suggest a common environmental toxicant(s) within the Streptomyces genus that causes dopaminergic neurodegeneration. It could also provide a possible explanation for diseases such as Parkinson’s disease (PD), which is widely accepted to have both genetic and environmental factors.
Differential root transcriptomics in a polyploid non-model crop: the importance of respiration during osmotic stress
Authors: Zorrilla-Fontanesi Yasmín , Rouard Mathieu , Cenci Alberto , Kissel Ewaut , Do Hien , Dubois Emeric , Nidelet Sabine , Roux Nicolas , Swennen Rony , Carpentier Sebastien Christian 
Published: March 2016

AbstractTo explore the transcriptomic global response to osmotic stress in roots, 18 mRNA-seq libraries were generated from three triploid banana genotypes grown under mild osmotic stress (5% PEG) and control conditions. Illumina sequencing produced 568 million high quality reads, of which 70–84% were mapped to the banana diploid reference genome. Using different uni- and multivariate statistics, 92 genes were commonly identified as differentially expressed in the three genotypes. Using our in house workflow to analyze GO enriched and underlying biochemical pathways, we present the general processes affected by mild osmotic stress in the root and focus subsequently on the most significantly overrepresented classes associated with: respiration, glycolysis and fermentation. We hypothesize that in fast growing and oxygen demanding tissues, mild osmotic stress leads to a lower energy level, which induces a metabolic shift towards (i) a higher oxidative respiration, (ii) alternative respiration and (iii) fermentation. To confirm the mRNA-seq results, a subset of twenty up-regulated transcripts were further analysed by RT-qPCR in an independent experiment at three different time points. The identification and annotation of this set of genes provides a valuable resource to understand the importance of energy sensing during mild osmotic stress.
In vitro model of bone to facilitate measurement of adhesion forces and super-resolution imaging of osteoclasts
Authors: Deguchi Takahiro , Alanne Maria H. , Fazeli Elnaz , Fagerlund Katja M. , Pennanen Paula , Lehenkari Petri , Hänninen Pekka E. , Peltonen Juha , Näreoja Tuomas 
Published: March 2016

AbstractTo elucidate processes in the osteoclastic bone resorption, visualise resorption and related actin reorganisation, a combination of imaging technologies and an applicablein vitromodel is needed. Nanosized bone powder from matching species is deposited on any biocompatible surface in order to form a thin, translucent, smooth and elastic representation of injured bone. Osteoclasts cultured on the layer expressed matching morphology to ones cultured on sawed cortical bone slices. Resorption pits were easily identified by reflectance microscopy. The coating allowed actin structures on the bone interface to be visualised with super-resolution microscopy along with a detailed interlinked actin networks and actin branching in conjunction with V-ATPase, dynamin and Arp2/3 at actin patches. Furthermore, we measured the timescale of an adaptive osteoclast adhesion to bone by force spectroscopy experiments on live osteoclasts with bone-coated AFM cantilevers. Utilising thein vitromodel and the advanced imaging technologies we localised immunofluorescence signals in respect to bone with high precision and detected resorption at its early stages. Put together, our data supports a cyclic model for resorption in human osteoclasts.
Macrophage activation and polarization modify P2X7 receptor secretome influencing the inflammatory process
Authors: de Torre-Minguela Carlos , Barberà-Cremades Maria , Gómez Ana I. , Martín-Sánchez Fátima , Pelegrín Pablo 
Published: March 2016

AbstractThe activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly of the NLRP3 inflammasome leading to the release of pro-inflammatory cytokines and the establishment of the inflammatory response. However, P2X7R signaling to the NLRP3 inflammasome is uncoupled on M2 macrophages without changes on receptor activation. In this study, we analyzed P2X7R secretome in wild-type and P2X7R-deficient macrophages polarized either to M1 or M2 and proved that proteins released after P2X7R stimulation goes beyond caspase-1 secretome. The characterization of P2X7R-secretome reveals a new function of this receptor through a fine-tuning of protein release. We found that P2X7R stimulation in macrophages is able to release potent anti-inflammatory proteins, such as Annexin A1, independently of their polarization state suggesting for first time a potential role for P2X7R during resolution of the inflammation and not linked to the release of pro-inflammatory cytokines. These results are of prime importance for the development of therapeutics targeting P2X7R.
Indole-3-Acetic Acid Produced by Burkholderia heleia Acts as a Phenylacetic Acid Antagonist to Disrupt Tropolone Biosynthesis in Burkholderia plantarii
Authors: Wang Mengcen , Tachibana Seiji , Murai Yuta , Li Li , Lau Sharon Yu Ling , Cao Mengchao , Zhu Guonian , Hashimoto Makoto , Hashidoko Yasuyuki 
Published: March 2016

AbstractBurkholderia heleia PAK1-2 is a potent biocontrol agent isolated from rice rhizosphere, as it prevents bacterial rice seedling blight disease caused by Burkholderia plantarii. Here, we isolated a non-antibacterial metabolite from the culture fluid of B. heleia PAK1-2 that was able to suppress B. plantarii virulence and subsequently identified as indole-3-acetic acid (IAA). IAA suppressed the production of tropolone in B. plantarii in a dose-dependent manner without any antibacterial and quorum quenching activity, suggesting that IAA inhibited steps of tropolone biosynthesis. Consistent with this, supplementing cultures of B. plantarii with either L-[ring-2H5]phenylalanine or [ring-2H2~5]phenylacetic acid revealed that phenylacetic acid (PAA), which is the dominant metabolite during the early growth stage, is a direct precursor of tropolone. Exposure of B. plantarii to IAA suppressed production of both PAA and tropolone. These data particularly showed that IAA produced by B. heleia PAK1-2 disrupts tropolone production during bioconversion of PAA to tropolone via the ring-rearrangement on the phenyl group of the precursor to attenuate the virulence of B. plantarii. B. heleia PAK1-2 is thus likely a microbial community coordinating bacterium in rhizosphere ecosystems, which never eliminates phytopathogens but only represses production of phytotoxins or bacteriocidal substances.
Deciphering the Potential Pharmaceutical Mechanism of Chinese Traditional Medicine (Gui-Zhi-Shao-Yao-Zhi-Mu) on Rheumatoid Arthritis
Authors: Huang Lin , Lv Qi , Xie Duoli , Shi Tieliu , Wen Chengping 
Published: March 2016

AbstractGui-Zhi-Shao-Yao-Zhi-Mu (GSZ) decoction is a Traditional Chinese Medicine (TCM) formula commonly used for the treatment of Rheumatoid Arthritis (RA). The therapeutic effect of GSZ for RA treatment is supported by our clinical retrospective study. To uncover the potential mechanism underlying GSZ formula, we identified 1,327 targets of 673 compounds from 9 herbs that involve in Fc epsilon RI signaling pathway and regulation of immunoglobulin production. Comparison between formula targets with 79 RA drug targets and 675 RA disease genes showed that formula targets covered 31.6% RA drug targets and 19.9% RA disease genes. Formula specific targets presented expression patterns highly similar to the disease genes and drug targets based on the expression profiles of RA samples. Investigation of 10 inferred gene clusters from expression profiles with a target association network revealed that formula specific targets directly or indirectly interacted with disease genes that were essential for immune related biological processes (e.g. inflammatory responses, treatment response of rheumatoid arthritis, etc.). Our result indicated that GSZ disrupted the RA disease dysfunction modules and restored homeostasis in the human body. The systemic approach to infer therapeutic mechanisms of GSZ for RA treatment provides a new insight in the understanding of this TCM formula.
Dispersal of Bacillus subtilis and its effect on strawberry phyllosphere microbiota under open field and protection conditions
Authors: Wei Feng , Hu Xiaoping , Xu Xiangming 
Published: March 2016

AbstractUsing biological control agents (BCAs) is an essential component of integrated pest and diseases management. Despite much research on biocontrol of plant diseases, success in field crops has been limited with most successes being achieved in greenhouse cultivation. This lack of success is often attributed to the complex ecological processes involved in biocontrol. We used next generation sequencing (NGS) technology to study environmental fate of Bacillus subtilis, a widely used BCA, focusing on its dispersal aspect in open field and under protection. The dispersal of B. subtilis was very limited, particularly under protection. The reduction in the BCA population size was relatively small within 8 days; indeed, no overall reduction in the relative abundance was observed under the protected condition. These results suggested that limited dispersal is probably the main reason for its variable (and often low) control efficacy under field conditions. Thus to increase biocontrol efficacy, it is necessary to frequently apply this BCA with the application interval depending on the growth rate of target host tissues. Phyllosphere microbiota differed significantly between plants grown in open field and under protection but were not greatly affected by the introduced BCA.
Rab14 limits the sorting of Glut4 from endosomes into insulin-sensitive regulated secretory compartments in adipocytes
Authors: Brewer Paul Duffield , Habtemichael Estifanos N. , Romenskaia Irina , Coster Adelle C.F. , Mastick Cynthia Corley 
Published: March 2016

Insulin increases glucose uptake by increasing the rate of exocytosis of the facilitative glucose transporter isoform 4 (Glut4) relative to its endocytosis. Insulin also releases Glut4 from highly insulin-regulated secretory compartments (GSVs or Glut4 storage vesicles) into constitutively cycling endosomes. Previously it was shown that both overexpression and knockdown of the small GTP-binding protein Rab14 decreased Glut4 translocation to the plasma membrane (PM). To determine the mechanism of this perturbation, we measured the effects of Rab14 knockdown on the trafficking kinetics of Glut4 relative to two proteins that partially co-localize with Glut4, the transferrin (Tf) receptor and low-density-lipoprotein-receptor-related protein 1 (LRP1). Our data support the hypothesis that Rab14 limits sorting of proteins from sorting (or ‘early’) endosomes into the specialized GSV pathway, possibly through regulation of endosomal maturation. This hypothesis is consistent with known Rab14 effectors. Interestingly, the insulin-sensitive Rab GTPase-activating protein Akt substrate of 160 kDa (AS160) affects both sorting into and exocytosis from GSVs. It has previously been shown that exocytosis of GSVs is rate-limited by Rab10, and both Rab10 and Rab14 are in vitro substrates of AS160. Regulation of both entry into and exit from GSVs by AS160 through sequential Rab substrates would provide a mechanism for the finely tuned ‘quantal’ increases in cycling Glut4 observed in response to increasing concentrations of insulin.
ATP increases the migration of microglia across the brain endothelial cell monolayer
Authors: Maeda Tomoji , Inagaki Manato , Fujita Yu , Kimoto Takehiro , Tanabe-Fujimura Chiaki , Zou Kun , Liu Junjun , Liu Shuyu , Komano Hiroto 
Published: March 2016

The cerebral microcapillary endothelium, known as the blood–brain barrier (BBB), acts as a barrier between the blood and the interstitial fluid of the brain. The BBB therefore controls the passage of nutrients into the central nervous system (CNS). Microglia show a specific affinity for migration into the CNS, and this migration appears to occur independently of BBB integrity. To study the migration of microglia across the BBB, we developed an in vitro co-culture system of mouse brain endothelial cells (MBECs) and Ra2 microglia using Transwell inserts. We first investigated the influence of microglia or ATP, a microglial chemotactic factor, on MBEC barrier integrity. The addition of microglia or ATP led to the disruption of the MBEC monolayer and significantly decreased barrier function as measured by trans-endothelial electrical resistance (TEER) and electric cell–substrate impedance sensing (ECIS). Furthermore, ATP promoted the migration of microglia but not macrophages across the MBEC monolayer. An inhibitor of matrix metalloproteinases (MMPs) decreased the transmigration of microglia in our system, indicating that MMPs play a role in microglial chemotaxis. We specifically identify a role for microglia-derived MMP-2. In conclusion, we offer evidence that microglia migration across the brain endothelial cell monolayer is increased in the presence of ATP in a manner that involves MMP secretion.
Long‐term stable 60 GHz optical two‐tone signal by destructive optical interference obtained from RF phase adjustment
Authors: Chiba A. , Akamatsu Y. , Takada K. 
Published: March 2016

An optical two‐tone signal with 60 GHz frequency spacing is experimentally demonstrated, by sinusoidally modulating two lightwaves with different modulation indices and RF phases. By superposing two modulation lightwaves with orthogonal polarisation, polarisation orthogonality is achieved between undesired low‐order optical sidebands and the desired high‐order optical sidebands together with the incident light‐wave. This enables us to suppress the undesired sidebands using polarisers instead of optical filter. Such operation has been implemented using optical modulator possessing RF ports for external termination, which is nested in one mode of polarisation‐maintaining Sagnac interferometer (PMSI). This implementation is equivalent to optical single‐sideband modulator, but required nested Mach–Zehnder structure is just one. Owing to this reduction together with use of one mode in PMSI, long‐term stable operation more than 6 h has been successfully obtained, with 29 dB suppression ratio of undesired first‐order sidebands against desired third‐order optical sidebands.
Combined effects of alpha particles and depleted uranium on Zebrafish ( Danio rerio ) embryos
Authors: Ng Candy Y.P. , Pereira Sandrine , Cheng Shuk Han , Adam-Guillermin Christelle , Garnier-Laplace Jacqueline , Yu Kwan Ngok 
Published: March 2016

Abstract
The combined effects of low-dose or high-dose alpha particles and depleted uranium (DU) in Zebrafish ( Danio rerio ) embryos were studied. Three schemes were examined—(i) [I L U L ]: 0.44 mGy alpha-particle dose + 10 µg/l DU exposure, (ii) [I H U H ]: 4.4 mGy alpha-particle dose + 100 µg/l DU exposure and (iii) [I H U L ]: 4.4 mGy alpha-particle dose + 10 µg/l DU exposure—in which Zebrafish embryos were irradiated with alpha particles at 5 h post fertilization (hpf) and/or exposed to uranium at 5–6 hpf. The results were also compared with our previous work, which studied the effects of [I L U H ]: 0.44 mGy alpha-particle dose + 100 µg/l DU exposure. When the Zebrafish embryos developed to 24 hpf, the apoptotic signals in the entire embryos, used as the biological endpoint for this study, were quantified. Our results showed that [I L U L ] and [I H U L ] led to antagonistic effects, whereas [I H U H ] led to an additive effect. The effect found for the previously studied case of [I L U H ] was difficult to define because it was synergistic with reference to the 100 µg/l DU exposure, but it was antagonistic with reference to the 0.44 mGy alpha-particle dose. All the findings regarding the four different schemes showed that the combined effects critically depended on the dose response to each individual stressor. We also qualitatively explained these findings in terms of promotion of early death of cells predisposed to spontaneous transformation by alpha particles, interacting with the delay in cell death resulting from various concentrations of DU exposure.