bluuebunny/crossref_metadata_2025_split huggingface dataset:
General hyperconcentration of photonic polarization-time-bin hyperentanglement assisted by nitrogen-vacancy centers coupled to resonators
Authors: Du Fang-Fang , Deng Fu-Guo , Long Gui-Lu 
Published: November 2016

AbstractEntanglement concentration protocol (ECP) is used to extract the maximally entangled states from less entangled pure states. Here we present a general hyperconcentration protocol for two-photon systems in partially hyperentangled Bell states that decay with the interrelation between the time-bin and the polarization degrees of freedom (DOFs), resorting to an input-output process with respect to diamond nitrogen-vacancy centers coupled to resonators. We show that the resource can be utilized sufficiently and the success probability is largely improved by iteration of the hyper-ECP process. Besides, our hyper-ECP can be directly extended to concentrate nonlocal partially hyperentangled N-photon Greenberger-Horne-Zeilinger states, and the success probability remains unchanged with the growth of the number of photons. Moreover, the time-bin entanglement is a useful DOF and it only requires one path for transmission, which means it not only economizes on a large amount of quantum resources but also relaxes from the path-length dispersion in long-distance quantum communication.
Modeled changes of cerebellar activity in mutant mice are predictive of their learning impairments
Authors: Badura Aleksandra , Clopath Claudia , Schonewille Martijn , De Zeeuw Chris I. 
Published: November 2016

AbstractTranslating neuronal activity to measurable behavioral changes has been a long-standing goal of systems neuroscience. Recently, we have developed a model of phase-reversal learning of the vestibulo-ocular reflex, a well-established, cerebellar-dependent task. The model, comprising both the cerebellar cortex and vestibular nuclei, reproduces behavioral data and accounts for the changes in neural activity during learning in wild type mice. Here, we used our model to predict Purkinje cell spiking as well as behavior before and after learning of five different lines of mutant mice with distinct cell-specific alterations of the cerebellar cortical circuitry. We tested these predictions by obtaining electrophysiological data depicting changes in neuronal spiking. We show that our data is largely consistent with the model predictions for simple spike modulation of Purkinje cells and concomitant behavioral learning in four of the mutants. In addition, our model accurately predicts a shift in simple spike activity in a mutant mouse with a brainstem specific mutation. This combination of electrophysiological and computational techniques opens a possibility of predicting behavioral impairments from neural activity.
A Presenilin/Notch1 pathway regulated by miR-375, miR-30a, and miR-34a mediates glucotoxicity induced-pancreatic beta cell apoptosis
Authors: Li Yating , Zhang Tao , Zhou Yuncai , Sun Yi , Cao Yue , Chang Xiaoai , Zhu Yunxia , Han Xiao 
Published: November 2016

AbstractThe presenilin-mediated Notch1 cleavage pathway plays a critical role in controlling pancreatic beta cell fate and survival. The aim of the present study was to investigate the role of Notch1 activation in glucotoxicity-induced beta cell impairment and the contributions of miR-375, miR-30a, and miR-34a to this pathway. We found that the protein levels of presenilins (PSEN1 and PSEN2), and NOTCH1 were decreased in INS-1 cells after treatment with increased concentrations of glucose, whereas no significant alteration of mRNA level of Notch1 was observed. Targeting of miR-375, miR-30a, and miR-34a to the 3′utr of Psen1, Psen2, and Notch1, respectively, reduced the amounts of relevant proteins, thereby reducing NICD1 amounts and causing beta cell apoptosis. Overexpression of NICD1 blocked the effects of glucotoxicity as well as miRNA overabundance. Downregulating the expression of miR-375, miR-30a, and miR-34a restored PSEN1, PSEN2, and NICD1 production and prevented glucotoxicity-induced impairment of the beta cells. These patterns of miRNA regulation of the Notch1 cleavage pathway were reproduced in GK rats as well as in aged rats. Our findings demonstrated that miRNA-mediated suppression of NICD1 links the presenilin/Notch1 pathway to glucotoxicity in mature pancreatic beta cells.
Keap1 hypomorphism protects against ischemic and obstructive kidney disease
Authors: Tan Roderick J. , Chartoumpekis Dionysios V. , Rush Brittney M. , Zhou Dong , Fu Haiyan , Kensler Thomas W. , Liu Youhua 
Published: November 2016

AbstractThe Keap1/Nrf2 pathway is a master regulator of antioxidant, anti-inflammatory, and other cytoprotective mechanisms important in protection from kidney disease. For the first time in kidney disease, we describe the use of Keap1 hypomorphic mice, which possess Nrf2 hyperactivation. We exposed these mice and wild type controls to ischemia/reperfusion injury (IRI). The initial tubular injury at 24 hours post-IRI appeared to be unaffected, with the only observed difference being a decrease in inflammatory cytokine expression in the hypomorphs. However, we noted significant improvement in serum creatinine in the hypomorphs at 3 and 10 days after injury, and renal fibrosis was dramatically attenuated at the late timepoint. Assessment of Nrf2-regulated targets (GSTM1, GSTP1, NQO1) revealed higher expression in the hypomorphs at baseline. While injury tended to suppress these genes in wild-type mice, the suppression was attenuated or reversed in Keap1 hypomorphs, suggesting that protection in these mice was mediated by increased Nrf2 transcriptional activity. To assess the generalizability of our findings, we subjected the hypomorphs to unilateral ureteral obstruction (UUO) and again found significant protection and increased expression of Nrf2 targets. Overall, these results support the conclusion that the Nrf2 pathway is protective in a variety of kidney diseases.
Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release
Authors: Xin Guang , Wei Zeliang , Ji Chengjie , Zheng Huajie , Gu Jun , Ma Limei , Huang Wenfang , Morris-Natschke Susan L. , Yeh Jwu-Lai , Zhang Rui , Qin Chaoyi , Wen Li , Xing Zhihua , Cao Yu , Xia Qing , Lu Yanrong , Li Ke , Niu Hai , Lee Kuo-Hsiung , Huang Wen 
Published: November 2016

AbstractThrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.
Understanding the immune system architecture and transcriptome responses to southern rice black-streaked dwarf virus in Sogatella furcifera
Authors: Wang Lin , Tang Nan , Gao Xinlei , Guo Dongyang , Chang Zhaoxia , Fu Yating , Akinyemi Ibukun A. , Wu Qingfa 
Published: November 2016

AbstractSogatella furcifera, the white-backed planthopper (WBPH), has become one of the most destructive pests in rice production owing to its plant sap-sucking behavior and efficient transmission of Southern rice black-streaked dwarf virus (SRBSDV) in a circulative, propagative and persistent manner. The dynamic and complex SRBSDV-WBPH-rice plant interaction is still poorly understood. In this study, based on a homology-based genome-wide analysis, 348 immune-related genes belonging to 28 families were identified in WBPH. A transcriptome analysis of non-viruliferous (NVF) and viruliferous groups with high viral titers (HVT) and median viral titers (MVT) revealed that feeding on SRBSDV-infected rice plants has a significant impact on gene expression, regardless of viral titers in insects. We identified 278 up-regulated and 406 down-regulated genes shared among the NVF, MVT, and HVT groups and detected significant down-regulation of primary metabolism-related genes and oxidoreductase. In viruliferous WBPH with viral titer-specific transcriptome changes, 1,906 and 1,467 genes exhibited strict monotonically increasing and decreasing expression, respectively. The RNAi pathway was the major antiviral response to increasing viral titers among diverse immune responses. These results clarify the responses of immune genes and the transcriptome of WBPH to SRBSDV and improve our knowledge of the functional relationship between pathogen, vector, and host.
Tumour microenvironment-responsive lipoic acid nanoparticles for targeted delivery of docetaxel to lung cancer
Authors: Gu Fenfen , Hu Chuling , Tai Zhongguang , Yao Chong , Tian Jing , Zhang Lijuan , Xia Qingming , Gong Chunai , Gao Yuan , Gao Shen 
Published: November 2016

AbstractIn the present study, we developed a novel type of reduction-sensitive nanoparticles (NPs) for docetaxel (DTX) delivery based on cross-linked lipoic acid NPs (LANPs). The physicochemical properties, cellular uptake and in vitro cytotoxicity of DTX loaded LANPs (DTX-LANPs) on A549 cells were investigated. Furthermore, the in vivo distribution and in vivo efficacy of DTX-LANPs was evaluated. The results showed that DTX-LANPs had a particle size of 110 nm and a negative zeta potential of −35 mv with excellent colloidal stability. LANPs efficiently encapsulated DTX with a high drug loading of 4.51% ± 0.49% and showed remarkable reduction-sensitive drug release in vitro. Cellular uptake experiments demonstrated that LANPs significantly increased intracellular DTX uptake by about 10 fold as compared with free DTX. The cytotoxicity of DTX-LANPs showed significantly higher potency in inhibiting A549 cell growth than free DTX, while blank LANPs had a good biocompatibility. In addition, in vivo experiments demonstrated that DTX-LANPs could enhance tumour targeting and anti-tumour efficacy with low systemic toxicity. In conclusion, LANPs may prove to be a potential tumour microenvironment-responsive delivery system for cancer treatment, with the potential for commercialization due to the simple component, controllable synthesis, stability and economy.
Isolation and mass spectrometry analysis of urinary extraexosomal proteins
Authors: Hildonen Siri , Skarpen Ellen , Halvorsen Trine Grønhaug , Reubsaet Léon 
Published: November 2016

AbstractThe aim of the present study was to develop a LC-MS/MS-based proteomic analysis method of urinary exosomal proteins that has the potential to discover disease biomarkers. In short, urinary exosomes from healthy subjects were isolated by immunocapture on magnetic beads, detected by immunofluorescence and TEM, trypsin digested directly on the beads for an accelerated time with no addition of detergents before performing an LC-MS analysis of the trypsinate. To our knowledge, this is the first proteomic analysis of proteins displayed on the outer surface of exosomes. The outer exosome proteome may contain proteins that are of higher biomarker value compared to soluble cargo protein as the proteins projecting into the extracellular milieu might be more directly involved in physiological functions of exosomes. The proteomic analysis identified 49 proteins that were considered significant; the majority is involved in carbohydrate and lipid metabolism or in immune responses. Thirty of the proteins are linked to diseases. The developed proteomic method exploiting urinary exosomes might be of great value in search for diagnostic or prognostic biomarkers of especially metabolic and immune-related diseases.
Genome-wide analyses reveal a highly conserved Dengue virus envelope peptide which is critical for virus viability and antigenic in humans
Authors: Fleith Renata C. , Lobo Francisco P. , dos Santos Paula F. , Rocha Mariana M. , Bordignon Juliano , Strottmann Daisy M. , Patricio Daniel O. , Pavanelli Wander R. , Lo Sarzi Maria , Santos Claudia N. D. , Ferguson Brian J. , Mansur Daniel S. 
Published: November 2016

AbstractTargeting regions of proteins that show a high degree of structural conservation has been proposed as a method of developing immunotherapies and vaccines that may bypass the wide genetic variability of RNA viruses. Despite several attempts, a vaccine that protects evenly against the four circulating Dengue virus (DV) serotypes remains elusive. To find critical conserved amino acids in dengue viruses, 120 complete genomes of each serotype were selected at random and used to calculate conservation scores for nucleotide and amino acid sequences. The identified peptide sequences were analysed for their structural conservation and localisation using crystallographic data. The longest, surface exposed, highly conserved peptide of Envelope protein was found to correspond to amino acid residues 250 to 270. Mutation of this peptide in DV1 was lethal, since no replication of the mutant virus was detected in human cells. Antibodies against this peptide were detected in DV naturally infected patients indicating its potential antigenicity. Hence, this study has identified a highly conserved, critical peptide in DV that is a target of antibodies in infected humans.
Adenovirally-Induced Polyfunctional T Cells Do Not Necessarily Recognize the Infected Target: Lessons from a Phase I Trial of the AERAS-402 Vaccine
Authors: Nyendak Melissa , Swarbrick Gwendolyn M. , Duncan Amanda , Cansler Meghan , Huff Ervina Winata , Hokey David , Evans Tom , Barker Lewellys , Blatner Gretta , Sadoff Jerald , Douoguih Macaya , Pau Maria Grazia , Lewinsohn Deborah A. , Lewinsohn David M. 
Published: November 2016

AbstractThe development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4+ and CD8+ T cell responses. However, analysis of the vaccine-induced CD8+ T cells revealed that in many instances these cells did not recognize the Mtb-infected cell. Our findings highlight the measurement of vaccine-induced, polyfunctional T cells may not reflect the extent or degree to which these cells are capable of identifying the Mtb-infected cell and correspondingly, the value of detailed experimental medicine studies early in vaccine development.
Contribution of Atmospheric Diffusion Conditions to the Recent Improvement in Air Quality in China
Authors: Wang Xiaoyan , Wang Kaicun , Su Liangyuan 
Published: November 2016

AbstractThis study analyzed hourly mass concentration observations of PM2.5 (particulate matters with diameter less than 2.5 μm) at 512 stations in China from December 2013 to May 2015. We found that the mean concentrations of PM2.5 during the winter and spring of 2015 Dec. 2014 to Feb. 2015 and Mar. 2015 to May 2015) decreased by 20% and 14% compared to the previous year, respectively. Hazardous air-quality days decreased by 11% in 2015 winter, with more frequent good to unhealthy days; and the good and moderate air-quality days in 2015 spring increased by 9% corresponding to the less occurrence of unhealthy conditions. We compared the atmospheric diffusion conditions during these two years and quantified its contribution to the improvement of air quality during the first half of 2015 over China. Our results show that during the 2015 winter and spring, 70% and 57% of the 512 stations experienced more favorable atmospheric diffusion conditions compared to those of previous year. Over central and northern China, approximately 40% of the total decrease in PM2.5 during the 2015 winter can be attributed to the favorable atmospheric diffusion conditions. The atmospheric diffusion conditions during the spring of 2015 were not as favorable as in winter; and the average contributions of the atmospheric conditions were slight.
A flexible triboelectric-piezoelectric hybrid nanogenerator based on P(VDF-TrFE) nanofibers and PDMS/MWCNT for wearable devices
Authors: Wang Xingzhao , Yang Bin , Liu Jingquan , Zhu Yanbo , Yang Chunsheng , He Qing 
Published: November 2016

AbstractThis paper studied and realized a flexible nanogenerator based on P(VDF-TrFE) nanofibers and PDMS/MWCNT thin composite membrane, which worked under triboelectric and piezoelectric hybrid mechanisms. The P(VDF-TrFE) nanofibers as a piezoelectric functional layer and a triboelectric friction layer are formed by electrospinning process. In order to improve the performance of triboelectric nanogenerator, the multiwall carbon nanotubes (MWCNT) is doped into PDMS patterned films as the other flexible friction layer to increase the initial capacitance. The flexible nanogenerator is fabricated by low cost MEMS processes. Its output performance is characterized in detail and structural optimization is performed. The device’s output peak-peak voltage, power and power density under triboelectric mechanism are 25 V, 98.56 μW and 1.98 mW/cm3 under the pressure force of 5 N, respectively. The output peak-peak voltage, power and power density under piezoelectric working principle are 2.5 V, 9.74 μW, and 0.689 mW/cm3 under the same condition, respectively. We believe that the proposed flexible, biocompatible, lightweight, low cost nanogenerator will supply effective power energy sustainably for wearable devices in practical applications.
Comprehensive DNA methylation analysis of the Aedes aegypti genome
Authors: Falckenhayn Cassandra , Carneiro Vitor Coutinho , de Mendonça Amarante Anderson , Schmid Katharina , Hanna Katharina , Kang Seokyoung , Helm Mark , Dimopoulos George , Fantappié Marcelo Rosado , Lyko Frank 
Published: November 2016

AbstractAedes aegypti mosquitoes are important vectors of viral diseases. Mosquito host factors play key roles in virus control and it has been suggested that dengue virus replication is regulated by Dnmt2-mediated DNA methylation. However, recent studies have shown that Dnmt2 is a tRNA methyltransferase and that Dnmt2-dependent methylomes lack defined DNA methylation patterns, thus necessitating a systematic re-evaluation of the mosquito genome methylation status. We have now searched the Ae. aegypti genome for candidate DNA modification enzymes. This failed to reveal any known (cytosine-5) DNA methyltransferases, but identified homologues for the Dnmt2 tRNA methyltransferase, the Mettl4 (adenine-6) DNA methyltransferase, and the Tet DNA demethylase. All genes were expressed at variable levels throughout mosquito development. Mass spectrometry demonstrated that DNA methylation levels were several orders of magnitude below the levels that are usually detected in organisms with DNA methylation-dependent epigenetic regulation. Furthermore, whole-genome bisulfite sequencing failed to reveal any evidence of defined DNA methylation patterns. These results suggest that the Ae. aegypti genome is unmethylated. Interestingly, additional RNA bisulfite sequencing provided first evidence for Dnmt2-mediated tRNA methylation in mosquitoes. These findings have important implications for understanding the mechanism of Dnmt2-dependent virus regulation.
Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii
Authors: Mengue Luce , Régnacq Matthieu , Aucher Willy , Portier Emilie , Héchard Yann , Samba-Louaka Ascel 
Published: November 2016

AbstractLegionella pneumophila is a ubiquitous, pathogenic, Gram-negative bacterium responsible for legionellosis. Like many other amoeba-resistant microorganisms, L. pneumophila resists host clearance and multiplies inside the cell. Through its Dot/Icm type IV secretion system, the bacterium injects more than three hundred effectors that modulate host cell physiology in order to promote its own intracellular replication. Here we report that L. pneumophila prevents proliferation of its natural host Acanthamoeba castellanii. Infected amoebae could not undergo DNA replication and no cell division was observed. The Dot/Icm secretion system was necessary for L. pneumophila to prevent the eukaryotic proliferation. The absence of proliferation was associated with altered amoebal morphology and with a decrease of mRNA transcript levels of CDC2b, a putative regulator of the A. castellanii cell cycle. Complementation of CDC28-deficient Saccharomyces cerevisiae by the CDC2b cDNA was sufficient to restore proliferation of CDC28-deficient S. cerevisiae and suggests for the first time that CDC2b from A. castellanii could be functional and a bona fide cyclin-dependent kinase. Hence, our results reveal that L. pneumophila impairs proliferation of A. castellanii and this effect could involve the cell cycle protein CDC2b.
The peacock train does not handicap cursorial locomotor performance
Authors: Thavarajah Nathan K. , Tickle Peter G. , Nudds Robert L. , Codd Jonathan R. 
Published: November 2016

AbstractExaggerated traits, like the peacock train, are recognized as classic examples of sexual selection. The evolution of sexual traits is often considered paradoxical as, although they enhance reproductive success, they are widely presumed to hinder movement and survival. Many exaggerated traits represent an additional mechanical load that must be carried by the animal and therefore may influence the metabolic cost of locomotion and constrain locomotor performance. Here we conducted respirometry experiments on peacocks and demonstrate that the exaggerated sexually selected train does not compromise locomotor performance in terms of the metabolic cost of locomotion and its kinematics. Indeed, peacocks with trains had a lower absolute and mass specific metabolic cost of locomotion. Our findings suggest that adaptations that mitigate any costs associated with exaggerated morphology are central in the evolution of sexually selected traits.
Mechanism of microtubule lumen entry for the α-tubulin acetyltransferase enzyme αTAT1
Authors: Coombes Courtney , Yamamoto Ami , McClellan Mark , Reid Taylor A. , Plooster Melissa , Luxton G. W. Gant , Alper Joshua , Howard Jonathon , Gardner Melissa K. 
Published: November 2016

Significance
αTAT1 is an enzyme that acetylates microtubules inside of cells, and acetylation is an important posttranslational microtubule modification. However, microtubules are long tubes, and the acetylation site for αTAT1 is on the inside of this tube. We investigated how αTAT1 enters the microtubule and moves around to access its acetylation sites once inside. We found that αTAT1 enters microtubules through its ends but does not move efficiently inside of the microtubule. However, a lowered affinity allows the enzyme to move more efficiently and leads to longer stretches of acetylation. Therefore, acetylation of microtubules could be controlled in the cell by modulating the affinity of αTAT1 for its acetylation site or increasing the number of microtubule ends.