bluuebunny/crossref_metadata_2025 huggingface dataset:
Allelopathic interactions of linoleic acid and nitric oxide increase the competitive ability of Microcystis aeruginosa
Authors: Song Hao , Lavoie Michel , Fan Xiaoji , Tan Hana , Liu Guangfu , Xu Pengfei , Fu Zhengwei , Paerl Hans W , Qian Haifeng
Published: April 2017

The frequency and intensity of cyanobacterial blooms are increasing worldwide with major societal and economic costs. Interactions between toxic cyanobacteria and eukaryotic algal competitors can affect toxic bloom formation, but the exact mechanisms of interspecies interactions remain unknown. Using metabolomic and proteomic profiling of co-cultures of the toxic cyanobacterium Microcystis aeruginosa with a green alga as well as of microorganisms collected in a Microcystis spp. bloom in Lake Taihu (China), we disentangle novel interspecies allelopathic interactions. We describe an interspecies molecular network in which M. aeruginosa inhibits growth of Chlorella vulgaris, a model green algal competitor, via the release of linoleic acid. In addition, we demonstrate how M. aeruginosa takes advantage of the cell signaling compound nitric oxide produced by C. vulgaris, which stimulates a positive feedback mechanism of linoleic acid release by M. aeruginosa and its toxicity. Our high-throughput system-biology approach highlights the importance of previously unrecognized allelopathic interactions between a broadly distributed toxic cyanobacterial bloom former and one of its algal competitors.
Nonlinear dynamics and chaos in an optomechanical beam
Authors: Navarro-Urrios Daniel , Capuj Néstor E. , Colombano Martín F. , García P. David , Sledzinska Marianna , Alzina Francesc , Griol Amadeu , Martínez Alejandro , Sotomayor-Torres Clivia M.
Published: April 2017

Optical nonlinearities, such as thermo-optic mechanisms and free-carrier dispersion, are often considered unwelcome effects in silicon-based resonators and, more specifically, optomechanical cavities, since they affect, for instance, the relative detuning between an optical resonance and the excitation laser. Here, we exploit these nonlinearities and their intercoupling with the mechanical degrees of freedom of a silicon optomechanical nanobeam to unveil a rich set of fundamentally different complex dynamics. By smoothly changing the parameters of the excitation laser we demonstrate accurate control to activate two- and four-dimensional limit cycles, a period-doubling route and a six-dimensional chaos. In addition, by scanning the laser parameters in opposite senses we demonstrate bistability and hysteresis between two- and four-dimensional limit cycles, between different coherent mechanical states and between four-dimensional limit cycles and chaos. Our findings open new routes towards exploiting silicon-based optomechanical photonic crystals as a versatile building block to be used in neurocomputational networks and for chaos-based applications.
Charge carrier mobility in thin films of organic semiconductors by the gated van der Pauw method
Authors: Rolin Cedric , Kang Enpu , Lee Jeong-Hwan , Borghs Gustaaf , Heremans Paul , Genoe Jan
Published: April 2017

Thin film transistors based on high-mobility organic semiconductors are prone to contact problems that complicate the interpretation of their electrical characteristics and the extraction of important material parameters such as the charge carrier mobility. Here we report on the gated van der Pauw method for the simple and accurate determination of the electrical characteristics of thin semiconducting films, independently from contact effects. We test our method on thin films of seven high-mobility organic semiconductors of both polarities: device fabrication is fully compatible with common transistor process flows and device measurements deliver consistent and precise values for the charge carrier mobility and threshold voltage in the high-charge carrier density regime that is representative of transistor operation. The gated van der Pauw method is broadly applicable to thin films of semiconductors and enables a simple and clean parameter extraction independent from contact effects.
Engineered probiotic Escherichia coli can eliminate and prevent Pseudomonas aeruginosa gut infection in animal models
Authors: Hwang In Young , Koh Elvin , Wong Adison , March John C. , Bentley William E. , Lee Yung Seng , Chang Matthew Wook
Published: April 2017

Bacteria can be genetically engineered to kill specific pathogens or inhibit their virulence. We previously developed a synthetic genetic system that allows a laboratory strain of Escherichia coli to sense and kill Pseudomonas aeruginosa in vitro. Here, we generate a modified version of the system, including a gene encoding an anti-biofilm enzyme, and use the probiotic strain Escherichia coli Nissle 1917 as host. The engineered probiotic shows in vivo prophylactic and therapeutic activity against P. aeruginosa during gut infection in two animal models (Caenorhabditis elegans and mice). These findings support the further development of engineered microorganisms with potential prophylactic and therapeutic activities against gut infections.
Cell state plasticity, stem cells, EMT, and the generation of intra-tumoral heterogeneity
Authors: Wahl Geoffrey M. , Spike Benjamin T.
Published: April 2017

Cellular heterogeneity in cancer represents a significant challenge. In order to develop effective and lasting therapies, it is essential to understand the source of this heterogeneity, and its role in tumor progression and therapy resistance. Here, we consider not only genetic and epigenetic mechanisms, but also inflammation and cell state reprogramming in creating tumor heterogeneity. We discuss similarities between normal mammary epithelial developmental states and various breast cancer molecular sub-types, and the cells that are thought to propagate them. We emphasize that while stem cell phenotypes and mesenchymal character have often been conflated, existing data suggest that the combination of intrinsic genetic and epigenetic changes, and microenvironmental influences generate multiple types of tumor propagating cells distinguishable by their positions along a continuum of epithelial to mesenchymal, stem to differentiated and embryonic to mature cell states. Consequently, in addition to the prospect of stem cell-directed tumor therapies, there is a need to understand interrelationships between stem cell, epithelial–mesenchymal, and tumor-associated reprogramming events to develop new therapies that mitigate cell state plasticity and minimize the evolution of tumor heterogeneity.
An alternative model for (breast) cancer predisposition
Authors: Teugels Erik , De Brakeleer Sylvia
Published: April 2017

While environmental factors can greatly increase cancer risk, it is clear that an individual’s genetic constitution has strong impact on tumor formation. Hereby we present an alternative cancer predisposition model built on the assumption that efficiencies of DNA maintenance mechanisms in normal cells are similar but not identical for each person. Small variations in an individual’s genetic constitution may result in slightly increased genomic instability and generate typical mutational signatures in normal cells. With recent and expected advances in the next-generation sequencing field, qualitative and quantitative establishment of such mutational signatures in normal tissue must become feasible, and may meanwhile provide a more accurate estimation of individual cancer risks, even in persons without familial antecedents. An additional advantage of this approach is that cancer risk assessment will not strictly rely on the individual’s genetic identity, but will also consider other factors (e.g., environmental and age) that can affect genomic integrity.
High probability of comorbidities in bronchial asthma in Germany
Authors: Heck S. , Al-Shobash S. , Rapp D. , Le D. D. , Omlor A. , Bekhit A. , Flaig M. , Al-Kadah B. , Herian W. , Bals R. , Wagenpfeil S. , Dinh Q. T.
Published: April 2017

Clinical experience has shown that allergic and non-allergic respiratory, metabolic, mental, and cardiovascular disorders sometimes coexist with bronchial asthma. However, no study has been carried out that calculates the chance of manifestation of these disorders with bronchial asthma in Saarland and Rhineland-Palatinate, Germany. Using ICD10 diagnoses from health care institutions, the present study systematically analyzed the co-prevalence and odds ratios of comorbidities in the asthma population in Germany. The odds ratios were adjusted for age and sex for all comorbidities for patients with asthma vs. without asthma. Bronchial asthma was strongly associated with allergic and with a lesser extent to non-allergic comorbidities: OR 7.02 (95%CI:6.83–7.22) for allergic rhinitis; OR 4.98 (95%CI:4.67–5.32) allergic conjunctivitis; OR 2.41 (95%CI:2.33–2.52) atopic dermatitis; OR 2.47 (95%CI:2.16–2.82) food allergy, and OR 1.69 (95%CI:1.61–1.78) drug allergy. Interestingly, increased ORs were found for respiratory diseases: 2.06 (95%CI:1.64–2.58) vocal dysfunction; 1.83 (95%CI:1.74–1.92) pneumonia; 1.78 (95%CI:1.73–1.84) sinusitis; 1.71 (95%CI:1.65–1.78) rhinopharyngitis; 2.55 (95%CI:2.03–3.19) obstructive sleep apnea; 1.42 (95%CI:1.25–1.61) pulmonary embolism, and 3.75 (95%CI:1.64–8.53) bronchopulmonary aspergillosis. Asthmatics also suffer from psychiatric, metabolic, cardiac or other comorbidities. Myocardial infarction (OR 0.86, 95%CI:0.79–0.94) did not coexist with asthma. Based on the calculated chances of manifestation for these comorbidities, especially allergic and respiratory, to a lesser extent also metabolic, cardiovascular, and mental disorders should be taken into consideration in the diagnostic and treatment strategy of bronchial asthma.
Heterologous prime-boost vaccination with H3N2 influenza viruses of swine favors cross-clade antibody responses and protection
Authors: Van Reeth Kristien , Mancera Gracia José Carlos , Trus Ivan , Sys Lieve , Claes Gerwin , Versnaeyen Han , Cox Eric , Krammer Florian , Qiu Yu
Published: April 2017

The emergence of multiple novel lineages of H1 and H3 influenza A viruses in swine has confounded control by inactivated vaccines. Because of substantial genetic and geographic heterogeneity among circulating swine influenza viruses, one vaccine strain per subtype cannot be efficacious against all of the current lineages. We have performed vaccination-challenge studies in pigs to examine whether priming and booster vaccinations with antigenically distinct H3N2 swine influenza viruses could broaden antibody responses and protection. We prepared monovalent whole inactivated, adjuvanted vaccines based on a European and a North American H3N2 swine influenza virus, which showed 81.5% aa homology in the HA1 region of the hemagglutinin and 83.4% in the neuraminidase. Our data show that (i) Priming with European and boosting with North American H3N2 swine influenza virus induces antibodies and protection against both vaccine strains, unlike prime-boost vaccination with a single virus or a single administration of bivalent vaccine. (ii) The heterologous prime-boost vaccination enhances hemagglutination inhibiting, virus neutralizing and neuraminidase inhibiting antibody responses against H3N2 viruses that are antigenically distinct from both vaccine strains. Antibody titers to the most divergent viruses were higher than after two administrations of bivalent vaccine. (iii) However, it does not induce antibodies to the conserved hemagglutinin stalk or to other hemagglutinin subtypes. We conclude that heterologous prime-boost vaccination might broaden protection to H3N2 swine influenza viruses and reduce the total amount of vaccine needed. This strategy holds potential for vaccination against influenza viruses from both humans and swine and for a better control of (reverse) zoonotic transmission of influenza viruses.
Vertex coloring of graphs via phase dynamics of coupled oscillatory networks
Authors: Parihar Abhinav , Shukla Nikhil , Jerry Matthew , Datta Suman , Raychowdhury Arijit
Published: April 2017

While Boolean logic has been the backbone of digital information processing, there exist classes of computationally hard problems wherein this paradigm is fundamentally inefficient. Vertex coloring of graphs, belonging to the class of combinatorial optimization, represents one such problem. It is well studied for its applications in data sciences, life sciences, social sciences and technology, and hence, motivates alternate, more efficient non-Boolean pathways towards its solution. Here we demonstrate a coupled relaxation oscillator based dynamical system that exploits insulator-metal transition in Vanadium Dioxide (VO2) to efficiently solve vertex coloring of graphs. Pairwise coupled VO2 oscillator circuits have been analyzed before for basic computing operations, but using complex networks of VO2 oscillators, or any other oscillators, for more complex tasks have been challenging in theory as well as in experiments. The proposed VO2 oscillator network harnesses the natural analogue between optimization problems and energy minimization processes in highly parallel, interconnected dynamical systems to approximate optimal coloring of graphs. We further indicate a fundamental connection between spectral properties of linear dynamical systems and spectral algorithms for graph coloring. Our work not only elucidates a physics-based computing approach but also presents tantalizing opportunities for building customized analog co-processors for solving hard problems efficiently.
Genome-wide detection of copy number variation in Chinese indigenous sheep using an ovine high-density 600 K SNP array
Authors: Ma Qing , Liu Xuexue , Pan Jianfei , Ma Lina , Ma Yuehui , He Xiaohong , Zhao Qianjun , Pu Yabin , Li Yingkang , Jiang Lin
Published: April 2017

Copy number variants (CNVs) represent a form of genomic structural variation underlying phenotypic diversity. In this study, we used the Illumina Ovine SNP 600 K BeadChip array for genome-wide detection of CNVs in 48 Chinese Tan sheep. A total of 1,296 CNV regions (CNVRs), ranging from 1.2 kb to 2.3 Mb in length, were detected, representing approximately 4.7% of the entire ovine genome (Oar_v3.1). We combined our findings with five existing CNVR reports to generate a composite genome-wide dataset of 4,321 CNVRs, which revealed 556 (43%) novel CNVRs. Subsequently, ten novel CNVRs were randomly chosen for further quantitative real-time PCR (qPCR) confirmation, and eight were successfully validated. Gene functional enrichment revealed that these CNVRs cluster into Gene Ontology (GO) categories of homeobox and embryonic skeletal system morphogenesis. One CNVR overlapping with the homeobox transcription factor DLX3 and previously shown to be associated with curly hair in sheep was identified as the candidate CNV for the special curly fleece phenotype in Tan sheep. We constructed a Chinese indigenous sheep genomic CNV map based on the Illumina Ovine SNP 600 K BeadChip array, providing an important addition to published sheep CNVs, which will be helpful for future investigations of the genomic structural variations underlying traits of interest in sheep.
Molecular diagnostic assays based on cpn60 UT sequences reveal the geographic distribution of subgroup 16SrXIII-(A/I)I phytoplasma in Mexico
Authors: Pérez-López Edel , Rodríguez-Martínez Douglas , Olivier Chrystel Y. , Luna-Rodríguez Mauricio , Dumonceaux Tim J.
Published: April 2017

Geographically diverse samples from strawberry exhibiting symptoms of Strawberry Green Petal (SbGP), periwinkle plants with virescence, and blackberry, blueberry, and raspberry plants displaying yellowing and inedible fruits, were assayed for the presence of phytoplasma DNA. PCR targeting the 16S rRNA-encoding gene and chaperonin-60 (cpn60) showed that the plants were infected with phytoplasma subgroup16SrXIII-(A/I)I (SbGP/MPV). To examine the geographic distribution of this pathogen in Mexico, we designed an array ofcpn60-targeted molecular diagnostic assays for SbGP/MPV phytoplasma. A fluorescent microsphere hybridization assay was designed that was capable of detecting SbGP/MPV phytoplasma in infected plant tissues, successfully differentiating it from other known phytoplasmacpn60 UT sequences, while identifying a double infection with SbGP/MPV and aster yellows (16SrI) phytoplasma. Two quantitative assays, quantitative real-time PCR (qRT-PCR) and droplet digital PCR (ddPCR), gave similar results in infected samples. Finally, a loop-mediated isothermal amplification (LAMP) assay provided rapid detection of SbGP/MPV phytoplasma DNA. Application of these assays revealed that SbGP/MPV phytoplasma is widely distributed in Central Mexico, with positive samples identified from eleven localities within three states separated by hundreds of kilometres. These results also provide tools for determining the presence and geographic distribution of this pathogen in plant and insect samples in other localities.
Light penetration-coupled photoisomerization modeling for photodeformation of diarylethene single crystal: upscaling isomerization to macroscopic deformation
Authors: Kim Muyoung , Yun Jung-Hoon , Cho Maenghyo
Published: April 2017

Diarylethene is one of the photo-responsive materials that show rapid and reversible changes in their color/electrochemical properties and macroscopic deformations in the crystalline phase by light irradiation. Photoisomerization is the main cause of the photo reactivity of diarylethene, and we established a statistical model based on the density matrix formalism, which predicts quantitative isomerization progress as a population term. The model reflects photo-switching properties of the target molecule, which were characterized by first principle calculations, and external stimulus factors (light irradiation conditions and temperature). By merging light penetration physics with the model, we derived light penetration depth dependent isomerization progress to theoretically investigate photodeformation of single crystal. The model well reproduced in-plane shear deformation under ultraviolet light irradiation which would provide guideline for photoactuator design. In addition, the statistical model addressed crucial findings (primary stimuli and molecular design parameter for increasing the isomerization rate, external stimuli enhancing fluorescence performance) itself.
Flow virometry analysis of envelope glycoprotein conformations on individual HIV virions
Authors: Arakelyan Anush , Fitzgerald Wendy , King Deborah F. , Rogers Paul , Cheeseman Hannah M. , Grivel Jean-Charles , Shattock Robin J. , Margolis Leonid
Published: April 2017

HIV-1 envelope proteins (Envs) play a critical role in HIV infection. In a correct trimeric conformation, Env mediates virus–cell binding and fusion. Malfunctioning of this machinery renders virions incapable of infecting cells. Each HIV-1 virion carries 10–14 Envs, and therefore a defective Env may not necessarily render a HIV virion non-infectious, since other Env on the same virion may still be functional. Alternatively, it is possible that on a given virion either all the spikes are defective or all are functional. Here, we investigate Env conformations on individual virions using our new nanotechnology, “flow virometry”, and a panel of antibodies that discriminate between various Env conformations. We found that the majority of HIV-1 virions carry either only trimeric (“functional”) or only defective spikes. The relatively small subfraction of virions that carry both functional and nonfunctional Envs contributes little to HIV infection of human lymphoid tissue ex vivo. The observation that the majority of virions exclusively express either functional or nonfunctional forms of Env has important implications for understanding the role of neutralizing and non-neutralizing antibodies in the immune control of HIV infection as well as for the development of effective prophylactic strategies.
Improving superconductivity in BaFe2As2-based crystals by cobalt clustering and electronic uniformity
Authors: Li L. , Zheng Q. , Zou Q. , Rajput S. , Ijaduola A. O. , Wu Z. , Wang X. P. , Cao H. B. , Somnath S. , Jesse S. , Chi M. , Gai Z. , Parker D. , Sefat A. S.
Published: April 2017

Quantum materials such as antiferromagnets or superconductors are complex in that chemical, electronic, and spin phenomena at atomic scales can manifest in their collective properties. Although there are some clues for designing such materials, they remain mainly unpredictable. In this work, we find that enhancement of transition temperatures in BaFe2As2-based crystals are caused by removing local-lattice strain and electronic-structure disorder by thermal annealing. While annealing improves Néel-ordering temperature in BaFe2As2 crystal (T
N
 = 132 K to 136 K) by improving in-plane electronic defects and reducing overall a-lattice parameter, it increases superconducting-ordering temperature in optimally cobalt-doped BaFe2As2 crystal (Tc = 23 to 25 K) by precipitating-out the cobalt dopants and giving larger overall a-lattice parameter. While annealing improves local chemical and electronic uniformity resulting in higher T
N
in the parent, it promotes nanoscale phase separation in the superconductor resulting in lower disparity and strong superconducting band gaps in the dominant crystal regions, which lead to both higher overall T
c
and critical-current-density, J
c
.
In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia
Authors: Dang Chung H. , Aubert Martine , De Silva Feelixge Harshana S. , Diem Kurt , Loprieno Michelle A. , Roychoudhury Pavitra , Stone Daniel , Jerome Keith R.
Published: April 2017

The ability to genetically manipulate trigeminal ganglion (TG) neurons would be useful in the study of the craniofacial nervous system and latent alphaherpesvirus infections. We investigated adeno-associated virus (AAV) vectors for gene delivery to the TG after intradermal whiskerpad delivery in mice. We demonstrated that AAV vectors of serotypes 1, 7, 8, and 9 trafficked from the whiskerpad into TG neurons and expressed transgenes within cell bodies and axons of sensory neurons in all three branches of the TG. Gene expression was highest with AAV1, and steadily increased over time up to day 28. Both constitutive and neuronal-specific promoters were able to drive transgene expression in TG neurons. Levels of vector genomes in the TG increased with input dose, and multiple transgenes could be co-delivered to TG neurons by separate AAV vectors. In conclusion, AAV1 vectors are suitable for gene delivery to TG sensory neurons following intradermal whiskerpad injection.
The glycogen synthase kinase MoGsk1, regulated by Mps1 MAP kinase, is required for fungal development and pathogenicity in Magnaporthe oryzae
Authors: Zhou Tengsheng , Dagdas Yasin F. , Zhu Xiaohan , Zheng Shiqin , Chen Liqiong , Cartwright Zachary , Talbot Nicholas J. , Wang Zonghua
Published: April 2017

Magnaporthe oryzae, the causal agent of blast disease, is one of the most destructive plant pathogens, causing significant yield losses on staple crops such as rice and wheat. The fungus infects plants with a specialized cell called an appressorium, whose development is tightly regulated by MAPK signaling pathways following the activation of upstream sensors in response to environmental stimuli. Here, we show the expression of the Glycogen synthase kinase 3 (GSK3) MoGSK1 in M. oryzae is regulated by Mps1 MAP kinase, particularly under the stressed conditions. Thus, MoGSK1 is functionally characterized in this study. MoGsk1 is functionally homologues to the Saccharomyces cerevisiae GSK3 homolog MCK1. Gene replacement of MoGSK1 caused significant delay in mycelial growth, complete loss of conidiation and inability to penetrate the host surface by mycelia-formed appressorium-like structures, consequently resulting in loss of pathogenicity. However, the developmental and pathogenic defects of Δmogsk1 are recovered via the heterologous expression of Fusarium graminearum GSK3 homolog gene FGK3, whose coding products also shows the similar cytoplasmic localization as MoGsk1 does in M. oryzae. By contrast, overexpression of MoGSK1 produced deformed appressoria in M. oryzae. In summary, our results suggest that MoGsk1, as a highly conservative signal modulator, dictates growth, conidiation and pathogenicity of M. oryzae.
Recovery of Alumina Nanocapacitors after High Voltage Breakdown
Authors: Belkin A. , Bezryadin A. , Hendren L. , Hubler A.
Published: April 2017

Breakdown of a dielectric material at high electric fields significantly limits the applicability of metal-dielectric-metal capacitors for energy storage applications. Here we demonstrate that the insulating properties of atomic-layer-deposited Al2O3thin films in Al/Al2O3/Al trilayers can recover after the breakdown. The recovery has been observed in samples with the dielectric thickness spanning from 4 to 9 nm. This phenomenon holds promise for a new generation of capacitors capable of restoring their properties after the dielectric breakdown. Also, if employed in capacitor banks, the recovery process will ensure that the bank remains operational even if a breakdown occurs.
Predicting the potential distribution in China of Euwallacea fornicatus (Eichhoff) under current and future climate conditions
Authors: Ge Xuezhen , Jiang Chao , Chen Linghong , Qiu Shuang , Zhao Yuxiang , Wang Tao , Zong Shixiang
Published: April 2017

Euwallacea fornicatus(Eichhoff) is an important forest pest that has caused serious damage in America and Vietnam. In 2014, it attacked forests ofAcer trialatumin the Yunnan province of China, creating concern in China’s Forestry Bureau. We used the CLIMEX model to predict and compare the potential distribution forE. fornicatesin China under current (1981–2010) and projected climate conditions (2011–2040) using one scenario (RCP8.5) and one global climate model (GCM), CSIRO-Mk3-6-0. Under both current and future climate conditions, the model predictedE. fornicatesto be mainly distributed in the south of China. Comparing distributions under both climate conditions showed that the area of potential distribution was projected to increase (mainly because of an increase in favourable habitat) and shift to the north. Our results help clarify the potential effect of climate change on the range of this forest pest and provide a reference and guide to facilitate its control in China.
Transcriptomic analysis reveals a previously unknown role for CD8+ T-cells in rVSV-EBOV mediated protection
Authors: Menicucci Andrea R. , Sureshchandra Suhas , Marzi Andrea , Feldmann Heinz , Messaoudi Ilhem
Published: April 2017

Ebola virus (EBOV) poses a significant threat to human health as highlighted by the recent epidemic in West Africa. Data from animal studies and a ring vaccination clinical trial conducted in Guinea during the recent epidemic demonstrated that a recombinant VSV where G protein is replaced with EBOV GP (rVSV-EBOV) is safe and highly efficacious. We previously established that antibodies are essential for rVSV-EBOV mediated protection against EBOV; however, the mechanisms by which this vaccine induces a humoral response and the role of T-cells in rVSV-EBOV mediated protection remain poorly understood. Since this is the only vaccine platform that has completed Phase III clinical studies, it is imperative to gain a better understanding of its mechanisms of protection. Therefore, we performed a longitudinal gene expression analysis of samples collected from controls and T-cell-depleted macaques after rVSV-EBOV vaccination and EBOV challenge. We show that rVSV-EBOV vaccination induces gene expression changes consistent with anti-viral immunity and B-cell proliferation. We also report a previously unappreciated role for CD8+ T-cells in mediating rVSV-EBOV protection. Finally, limited viral transcription in surviving animals may boost protective responses after EBOV challenge by maintaining transcriptional changes. This study presents a novel approach in determining mechanisms of vaccine efficacy.
Direct recognition of LPS drive TLR4 expressing CD8+ T cell activation in patients with rheumatoid arthritis
Authors: Tripathy Archana , Khanna Shweta , Padhan Prasanta , Smita Shuchi , Raghav Sunil , Gupta Bhawna
Published: April 2017

Aberrant immune responses characterize autoimmune disorders like Rheumatoid Arthritis (RA) wherein lymphocytes are recognized as key players. Role of CD8+T cells in RA has been less defined however we found that these cells are activated in RA patients with increased expression of cytolytic granules and inflammatory mediators thereby modulating immune responses contributing to disease severity. Though unconventional expression of different Toll Like Receptors (TLRs) on CD8+T cells has been proposed but their expression and role in T cell activation and differentiation in RA still remains obscure. Herein we report, for the first time, an increased expression of TLR4 on peripheral CD8+T cells of RA patients and its role in skewing CD8+T cells towards activated and inflammatory phenotype thereby playing a significant role in pathogenesis and progression of RA. We found that the surface expression of TLR4 on CD8+T cells directly correlates with disease severity. Moreover, these CD8+T cells respond to the TLR4 ligand LPS and express robust amounts of cytotolytic and inflammatory molecules including TNFα and IFNγ. Our study hence identifies an important role for CD8+T cells in orchestrating RA through TLR4 mediated activation and differentiation.
The Time Course of Spatial Attention Shifts in Elementary Arithmetic
Authors: Liu Dixiu , Cai Danni , Verguts Tom , Chen Qi
Published: April 2017

It has been proposed that elementary arithmetic induces spatial shifts of attention. However, the timing of this arithmetic-space association remains unknown. Here we investigate this issue with a target detection paradigm. Detecting targets in the right visual field was faster than in the left visual field when preceded by an addition operation, while detecting targets in the left visual field was faster than in the right visual field when preceded by a subtraction operation. The arithmetic-space association was found both at the end of the arithmetic operation and during calculation. In contrast, the processing of operators themselves did not induce spatial biases. Our results suggest that the arithmetic-space association resides in the mental arithmetic operation rather than in the individual numbers or the operators. Moreover, the temporal course of this effect was different in addition and subtraction.
The role of the brown adipose tissue in β3-adrenergic receptor activation-induced sleep, metabolic and feeding responses
Authors: Szentirmai Éva , Kapás Levente
Published: April 2017

Brown adipose tissue (BAT) is regulated by the sympathetic nervous system via β3-adrenergic receptors (β3-AR). Here we tested the hypothesis that pharmacological stimulation of β3-ARs leads to increased sleep in mice and if this change is BAT dependent. In wild-type (WT) animals, administration of CL-316,243, a selective β3-AR agonist, induced significant increases in non-rapid-eye movement sleep ﻿(NREMS) lasting for 4–10 h. Simultaneously, electroencephalographic slow-wave activity (SWA) was significantly decreased and body temperature was increased with a delay of 5–6 h. In uncoupling protein 1 (UCP-1) knockout mice, the middle and highest doses of the β3-AR agonist increased sleep and suppressed SWA, however, these effects were significantly attenuated and shorter-lasting as compared to WT animals. To determine if somnogenic signals arising from BAT in response to β3-AR stimulation are mediated by the sensory afferents of BAT, we tested the effects of CL-316,243 in mice with the chemical deafferentation of the intra-scapular BAT pads. Sleep responses to CL-316,243 were attenuated by ~50% in intra-BAT capsaicin-treated mice. Present findings indicate that the activation of BAT via β3-AR leads to increased sleep in mice and that this effect is dependent on the presence of UCP-1 protein and sleep responses require the intact sensory innervation of BAT.
Network-assisted analysis of GWAS data identifies a functionally-relevant gene module for childhood-onset asthma
Authors: Liu Y. , Brossard M. , Sarnowski C. , Vaysse A. , Moffatt M. , Margaritte-Jeannin P. , Llinares-López F. , Dizier M. H. , Lathrop M. , Cookson W. , Bouzigon E. , Demenais F.
Published: April 2017

The number of genetic factors associated with asthma remains limited. To identify new genes with an undetected individual effect but collectively influencing asthma risk, we conducted a network-assisted analysis that integrates outcomes of genome-wide association studies (GWAS) and protein-protein interaction networks. We used two GWAS datasets, each consisting of the results of a meta-analysis of nine childhood-onset asthma GWASs (5,924 and 6,043 subjects, respectively). We developed a novel method to compute gene-level P-values (fastCGP), and proposed a parallel dense-module search and cross-selection strategy to identify an asthma-associated gene module. We identified a module of 91 genes with a significant joint effect on childhood-onset asthma (P < 10−5). This module contained a core subnetwork including genes at known asthma loci and five peripheral subnetworks including relevant candidates. Notably, the core genes were connected to APP (encoding amyloid beta precursor protein), a major player in Alzheimer’s disease that is known to have immune and inflammatory components. Functional analysis of the module genes revealed four gene clusters involved in innate and adaptive immunity, chemotaxis, cell-adhesion and transcription regulation, which are biologically meaningful processes that may underlie asthma risk. Our findings provide important clues for future research into asthma aetiology.
Treatment of donor corneal tissue with immunomodulatory cytokines: a novel strategy to promote graft survival in high-risk corneal transplantation
Authors: Tahvildari Maryam , Emami-Naeini Parisa , Omoto Masahiro , Mashaghi Alireza , Chauhan Sunil K. , Dana Reza
Published: April 2017

Antigen-presenting cells (APCs) play an important role in transplant rejection and tolerance. In high-risk corneal transplantation, where the graft bed is inflamed and vascularized, immature APCs in the donor corneal stroma quickly mature and migrate to lymphoid tissues to sensitize host T cells. In this study, using a mouse model of corneal transplantation, we investigated whether enrichment of tolerogenic APCs (tolAPCs) in donor corneas can enhance graft survival in corneal allograft recipients with inflamed graft beds. Treatment of donor corneas with interleukin-10 (IL-10) and transforming growth factor-β1 (TGFβ1) altered the phenotype and function of tissue-residing APCs. Transplantation of these tolAPC-enriched corneas decreased frequencies of interferon gamma (IFNγ)+ effector T cells (Teffs), as well as allosensitization in the hosts, diminished graft infiltration of CD45+ and CD4+ cells, and significantly improved corneal allograft survival compared to saline-injected controls. These data provide a novel approach for tolAPC-based immunotherapy in transplantation by direct cytokine conditioning of the donor tissue.
Elucidation of quantitative structural diversity of remarkable rearrangement regions, shufflons, in IncI2 plasmids
Authors: Sekizuka Tsuyoshi , Kawanishi Michiko , Ohnishi Mamoru , Shima Ayaka , Kato Kengo , Yamashita Akifumi , Matsui Mari , Suzuki Satowa , Kuroda Makoto
Published: April 2017

A multiple DNA inversion system, the shufflon, exists in incompatibility (Inc) I1 and I2 plasmids. The shufflon generates variants of the PilV protein, a minor component of the thin pilus. The shufflon is one of the most difficult regions for de novo genome assembly because of its structural diversity even in an isolated bacterial clone. We determined complete genome sequences, including those of IncI2 plasmids carrying mcr-1, of three Escherichia coli strains using single-molecule, real-time (SMRT) sequencing and Illumina sequencing. The sequences assembled using only SMRT sequencing contained misassembled regions in the shufflon. A hybrid analysis using SMRT and Illumina sequencing resolved the misassembled region and revealed that the three IncI2 plasmids, excluding the shufflon region, were highly conserved. Moreover, the abundance ratio of whole-shufflon structures could be determined by quantitative structural variation analysis of the SMRT data, suggesting that a remarkable heterogeneity of whole-shufflon structural variations exists in IncI2 plasmids. These findings indicate that remarkable rearrangement regions should be validated using both long-read and short-read sequencing data and that the structural variation of PilV in the shufflon might be closely related to phenotypic heterogeneity of plasmid-mediated transconjugation involved in horizontal gene transfer even in bacterial clonal populations.
Unified Alignment of Protein-Protein Interaction Networks
Authors: Malod-Dognin Noël , Ban Kristina , Pržulj Nataša
Published: April 2017

Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.
Temperature-dependent folding allows stable dimerization of secretory and virus-associated E proteins of Dengue and Zika viruses in mammalian cells
Authors: Slon Campos J. L. , Marchese S. , Rana J. , Mossenta M. , Poggianella M. , Bestagno M. , Burrone O. R.
Published: April 2017

Dengue and Zika are two of the most important human viral pathogens worldwide. In both cases, the envelope glycoprotein E is the main target of the antibody response. Recently, new complex quaternary epitopes were identified which are the consequence of the arrangement of the antiparallel E dimers on the viral surface. Such epitopes can be exploited to develop more efficient cross-neutralizing vaccines. Here we describe a successful covalent stabilization of E dimers from Dengue and Zika viruses in mammalian cells. Folding and dimerization of secretory E was found to be strongly dependent on temperature but independent of PrM co-expression. In addition, we found that, due to the close relationship between flaviviruses, Dengue and Zika viruses E proteins can form heterodimers and assemble into mosaic viral particles. Finally, we present new virus-free analytical platforms to study and screen antibody responses against Dengue and Zika, which allow for differentiation of epitopes restricted to specific domains, dimers and higher order arrangements of E.
Neurons Export Extracellular Vesicles Enriched in Cysteine String Protein and Misfolded Protein Cargo
Authors: Deng Jingti , Koutras Carolina , Donnelier Julien , Alshehri Mana , Fotouhi Maryam , Girard Martine , Casha Steve , McPherson Peter S. , Robbins Stephen M. , Braun Janice E. A.
Published: April 2017

The fidelity of synaptic transmission depends on the integrity of the protein machinery at the synapse. Unfolded synaptic proteins undergo refolding or degradation in order to maintain synaptic proteostasis and preserve synaptic function, and buildup of unfolded/toxic proteins leads to neuronal dysfunction. Many molecular chaperones contribute to proteostasis, but one in particular, cysteine string protein (CSPα), is critical for proteostasis at the synapse. In this study we report that exported vesicles from neurons contain CSPα. Extracellular vesicles (EV’s) have been implicated in a wide range of functions. However, the functional significance of neural EV’s remains to be established. Here we demonstrate that co-expression of CSPα with the disease-associated proteins, polyglutamine expanded protein 72Q huntingtinex°n1 or superoxide dismutase-1 (SOD-1G93A) leads to the cellular export of both 72Q huntingtinex°n1 and SOD-1G93A via EV’s. In contrast, the inactive CSPαHPD-AAA mutant does not facilitate elimination of misfolded proteins. Furthermore, CSPα-mediated export of 72Q huntingtinex°n1 is reduced by the polyphenol, resveratrol. Our results indicate that by assisting local lysosome/proteasome processes, CSPα-mediated removal of toxic proteins via EVs plays a central role in synaptic proteostasis and CSPα thus represents a potential therapeutic target for neurodegenerative diseases.
Power Flow in a Large-Core Multimode Fiber under External Perturbation and its Applications
Authors: Qian Sen , Xu Yang , Zhong Lisheng , Su Lei
Published: April 2017

Large core optical multimode fiber provides benefits such as a large light-coupling tolerance, easy handling, and delivery of higher light power without undesirable nonlinear effects. In this research, we exploit the effects of external perturbation on the power flow within the large core fiber and present two relevant applications, namely a perturbation sensor and a doughnut beam tuner. Since conventional multimode fiber power flow model does not take into consideration the perturbation effect, we modify the power flow model so that the influence of time varying perturbation can be theoretically analyzed. Based on our theory, we further conduct the numerical simulation and experiments on these two applications. For the fiber vibration sensor, the proposed numerical model shows that the sensor sensitivity depends on the intensity profile of the launched beam and also the higher-order harmonics that were not reported previously can become interferences to affect the signal. For the beam tuner application, we prove both theoretically and experimentally that the doughnut intensity profile at the fiber output can be tuned in real-time by applying external perturbations to the fiber. We expect that the results can be useful to further exploit the external perturbation on large core fiber in various applications.
The tarantula toxin β/δ-TRTX-Pre1a highlights the importance of the S1-S2 voltage-sensor region for sodium channel subtype selectivity
Authors: Wingerd Joshua S. , Mozar Christine A. , Ussing Christine A. , Murali Swetha S. , Chin Yanni K.-Y. , Cristofori-Armstrong Ben , Durek Thomas , Gilchrist John , Vaughan Christopher W. , Bosmans Frank , Adams David J. , Lewis Richard J. , Alewood Paul F. , Mobli Mehdi , Christie Macdonald J. , Rash Lachlan D.
Published: April 2017

Voltage-gated sodium (NaV) channels are essential for the transmission of pain signals in humans making them prime targets for the development of new analgesics. Spider venoms are a rich source of peptide modulators useful to study ion channel structure and function. Here we describe β/δ-TRTX-Pre1a, a 35-residue tarantula peptide that selectively interacts with neuronal NaV channels inhibiting peak current of hNaV1.1, rNaV1.2, hNaV1.6, and hNaV1.7 while concurrently inhibiting fast inactivation of hNaV1.1 and rNaV1.3. The DII and DIV S3-S4 loops of NaV channel voltage sensors are important for the interaction of Pre1a with NaV channels but cannot account for its unique subtype selectivity. Through analysis of the binding regions we ascertained that the variability of the S1-S2 loops between NaV channels contributes substantially to the selectivity profile observed for Pre1a, particularly with regards to fast inactivation. A serine residue on the DIV S2 helix was found to be sufficient to explain Pre1a’s potent and selective inhibitory effect on the fast inactivation process of NaV1.1 and 1.3. This work highlights that interactions with both S1-S2 and S3-S4 of NaV channels may be necessary for functional modulation, and that targeting the diverse S1-S2 region within voltage-sensing domains provides an avenue to develop subtype selective tools.
Paper strip-embedded graphene quantum dots: a screening device with a smartphone readout
Authors: Álvarez-Diduk Ruslan , Orozco Jahir , Merkoçi Arben
Published: April 2017

Simple, inexpensive and rapid sensing systems are very demanded for a myriad of uses. Intrinsic properties of emerging paper-based analytical devices have demonstrated considerable potential to fulfill such demand. This work reports an easy-to-use, low cost, and disposable paper-based sensing device for rapid chemical screening with a smartphone readout. The device comprises luminescent graphene quantum dots (GQDs) sensing probes embedded into a nitrocellulose matrix where the resonance energy transfer phenomenon seems to be the sensing mechanism. The GQDs probes were synthesized from citric acid by a pyrolysis procedure, further physisorbed and confined into small wax-traced spots on the nitrocellulose substrate. The GQDs were excited by an UV LED, this, is powered by a smartphone used as both; energy source and imaging capture. The LED was contained within a 3D-printed dark chamber that isolates the paper platform from external light fluctuations leading to highly reproducible data. The cellulose-based device was proven as a promising screening tool for phenols and polyphenols in environmental and food samples, respectively. It opens up new opportunities for simple and fast screening of organic compounds and offers numerous possibilities for versatile applications. It can be especially useful in remote settings where sophisticated instrumentation is not always available.
Evolution of crystal structures in GeTe during phase transition
Authors: Jeong Kwangsik , Park Seungjong , Park Dambi , Ahn Min , Han Jeonghwa , Yang Wonjun , Jeong Hong-Sik , Cho Mann-Ho
Published: April 2017

We investigated changes in the crystal structure of GeTe during its phase transition. Using density functional theory (DFT) calculations, four possible crystal structures were identified: R3m, P1, Cm, and Fm3m. Among these, P1 and Cm were examined here for the first time. By calculating the internal energy of the crystal volume change, we verified that P1, R3m, and Cm can coexist in crystalline GeTe. The X-ray diffraction spectra of annealed and laser-irradiated GeTe films revealed coexisting P1 or R3m and Cm. In addition, we confirmed that Cm transforms into P1 or R3m after laser irradiation. The presence of these new structures was revealed in the crystal Raman spectra. Many of the Raman peaks in the crystalized GeTe could be explained by the coexistence of various structures. By calculating the band gaps of these structures, we also found that a structural transformation induces a change in the crystal resistance, owing to differences in the band gaps of individual structures. The generation of new crystal structures suggests a facile phase change and instability during the structural transformation.