bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optogenetic control of RhoA reveals zyxin-mediated elasticity of stress fibres
Authors: Oakes Patrick W. , Wagner Elizabeth , Brand Christoph A. , Probst Dimitri , Linke Marco , Schwarz Ulrich S. , Glotzer Michael , Gardel Margaret L. 
Published: June 2017

AbstractCytoskeletal mechanics regulates cell morphodynamics and many physiological processes. While contractility is known to be largely RhoA-dependent, the process by which localized biochemical signals are translated into cell-level responses is poorly understood. Here we combine optogenetic control of RhoA, live-cell imaging and traction force microscopy to investigate the dynamics of actomyosin-based force generation. Local activation of RhoA not only stimulates local recruitment of actin and myosin but also increased traction forces that rapidly propagate across the cell via stress fibres and drive increased actin flow. Surprisingly, this flow reverses direction when local RhoA activation stops. We identify zyxin as a regulator of stress fibre mechanics, as stress fibres are fluid-like without flow reversal in its absence. Using a physical model, we demonstrate that stress fibres behave elastic-like, even at timescales exceeding turnover of constituent proteins. Such molecular control of actin mechanics likely plays critical roles in regulating morphodynamic events.
Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase
Authors: Hutchinson Jonathan P. , Rowland Paul , Taylor Mark R. D. , Christodoulou Erica M. , Haslam Carl , Hobbs Clare I. , Holmes Duncan S. , Homes Paul , Liddle John , Mole Damian J. , Uings Iain , Walker Ann L. , Webster Scott P. , Mowat Christopher G. , Chung Chun-wa 
Published: June 2017

AbstractKynurenine-3-monooxygenase (KMO) is a key FAD-dependent enzyme of tryptophan metabolism. In animal models, KMO inhibition has shown benefit in neurodegenerative diseases such as Huntington’s and Alzheimer’s. Most recently it has been identified as a target for acute pancreatitis multiple organ dysfunction syndrome (AP-MODS); a devastating inflammatory condition with a mortality rate in excess of 20%. Here we report and dissect the molecular mechanism of action of three classes of KMO inhibitors with differentiated binding modes and kinetics. Two novel inhibitor classes trap the catalytic flavin in a previously unobserved tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production seen with previous substrate site inhibitors. These structural and mechanistic insights culminated in GSK065(C1) and GSK366(C2), molecules suitable for preclinical evaluation. Moreover, revising the repertoire of flavin dynamics in this enzyme class offers exciting new opportunities for inhibitor design.
Differential processing of thalamic information via distinct striatal interneuron circuits
Authors: Assous Maxime , Kaminer Jaime , Shah Fulva , Garg Arpan , Koós Tibor , Tepper James M. 
Published: June 2017

AbstractRecent discoveries of striatal GABAergic interneurons require a new conceptualization of the organization of intrastriatal circuitry and their cortical and thalamic inputs. We investigated thalamic inputs to the two populations of striatal neuropeptide Y (NPY) interneurons, plateau low threshold spike (PLTS) and NPY-neurogliaform (NGF) cells. Optogenetic activation of parafascicular inputs evokes suprathreshold monosynaptic glutamatergic excitation in NGF interneurons and a disynaptic, nicotinic excitation through cholinergic interneurons. In contrast, the predominant response of PLTS interneurons is a disynaptic inhibition dependent on thalamic activation of striatal tyrosine hydroxylase interneurons (THINs). In contrast, THINs do not innervate NGF or fast spiking interneurons, showing significant specificity in THINs outputs. Chemospecific ablation of THINs impairs prepulse inhibition of the acoustic startle response suggesting an important behavioural role of this disynaptic pathway. Our findings demonstrate that the impact of the parafascicular nucleus on striatal activity and some related behaviour critically depend on synaptic interactions within interneuronal circuits.
The deubiquitinating enzymes USP4 and USP17 target hyaluronan synthase 2 and differentially affect its function
Authors: Mehić M , de Sa V K , Hebestreit S , Heldin C-H , Heldin P 
Published: June 2017

AbstractThe levels of hyaluronan, a ubiquitous glycosaminoglycan prominent in the extracellular matrix, is balanced through the actions of hyaluronan-synthesizing enzymes (HAS1, 2 and 3) and degrading hyaluronidases (Hyal 1, 2, 3 and PH20). Hyaluronan accumulates in rapidly remodeling tissues, such as breast cancer, due to deregulated expression of the HAS2 gene and/or alterations of HAS2 activity. The activity of HAS2 is regulated by post-translational modifications, including ubiquitination. In order to identify deubiquitinating enzymes (DUBs) that are involved in de-ubiquitination of HAS2, a complementary (cDNA) library of 69 Flag-HA-tagged human DUBs cloned into retroviral vectors was screened in human embryonic kidney (HEK) 293T cells for their ability to de-ubiquitinate myc-tagged HAS2. Several DUBs were found to decrease the ubiquitination of 6myc-HAS2, among which, the most effective were USP17 and USP4. USP17 efficiently removed polyubiquitination, whereas USP4 preferentially removed monoubiquitination of 6myc-HAS2. Co-immunoprecipitation studies revealed interactions between HAS2 and USP17, as well as between HAS2 and USP4, in membrane preparations of HEK293T cells. USP17 significantly stabilized 6myc-HAS2 protein levels, whereas USP4 did not. The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. In conclusion, USP17 and USP4 differently affect HAS2 ubiquitination, and the stability and function of HAS2.
High-dimensional quantum key distribution based on multicore fiber using silicon photonic integrated circuits
Authors: Ding Yunhong , Bacco Davide , Dalgaard Kjeld , Cai Xinlun , Zhou Xiaoqi , Rottwitt Karsten , Oxenløwe Leif Katsuo 
Published: June 2017

AbstractQuantum key distribution provides an efficient means to exchange information in an unconditionally secure way. Historically, quantum key distribution protocols have been based on binary signal formats, such as two polarization states, and the transmitted information efficiency of the quantum key is intrinsically limited to 1 bit/photon. Here we propose and experimentally demonstrate, for the first time, a high-dimensional quantum key distribution protocol based on space division multiplexing in multicore fiber using silicon photonic integrated lightwave circuits. We successfully realized three mutually unbiased bases in a four-dimensional Hilbert space, and achieved low and stable quantum bit error rate well below both the coherent attack and individual attack limits. Compared to previous demonstrations, the use of a multicore fiber in our protocol provides a much more efficient way to create high-dimensional quantum states, and enables breaking the information efficiency limit of traditional quantum key distribution protocols. In addition, the silicon photonic circuits used in our work integrate variable optical attenuators, highly efficient multicore fiber couplers, and Mach-Zehnder interferometers, enabling manipulating high-dimensional quantum states in a compact and stable manner. Our demonstration paves the way to utilize state-of-the-art multicore fibers for noise tolerance high-dimensional quantum key distribution, and boost silicon photonics for high information efficiency quantum communications.
Clinical Efficacy and Post-Treatment Seromarkers Associated with the Risk of Hepatocellular Carcinoma among Chronic Hepatitis C Patients
Authors: Lee Mei-Hsuan , Huang Chung-Feng , Lai Hsueh-Chou , Lin Chun-Yen , Dai Chia-Yen , Liu Chun-Jen , Wang Jing-Houng , Huang Jee-Fu , Su Wen-Pang , Yang Hung-Chih , Kee Kwong-Ming , Yeh Ming-Lun , Chuang Po-Heng , Hsu Shih-Jer , Huang Ching-I , Kao Jung-Ta , Chen Chieh-Chang , Chen Sheng-Hung , Jeng Wen-Juei , Yang Hwai-I , Yuan Yong , Lu Sheng-Nan , Sheen I-Shyan , Liu Chen-Hua , Peng Cheng-Yuan , Kao Jia-Horng , Yu Ming-Lung , Chuang Wan-Long , Chen Chien-Jen 
Published: June 2017

AbstractThis follow-up study enrolled chronic hepatitis C patients to evaluate the treatment efficacy and to identify post-treatment seromarkers associated with risk of hepatocellular carcinoma (HCC) among patients with a sustained virological response (SVR) or nonsustained virological response (NSVR). A total of 4639 patients who received pegylated interferon and ribavirin during 2004–2013 were followed until December 2014. HCC was confirmed through health examinations and data linkage with a national database. A total of 233 HCC cases were reported after 26,163 person-years of follow-up, indicating an incidence of 8.9 per 1000 person-years: 6.9 for SVR and 21.6 for NSVR per 1000 person-years. The associated risk of HCC in patients with SVR was 0.37 (0.22–0.63) for those without cirrhosis and 0.54 (0.31–0.92) for those with cirrhosis compared with their respective counterparts with NSVR. Among patients with SVR, advanced age, male gender, cirrhosis, decreased platelet count, and increased aspartate aminotransferase and α-fetoprotein levels were associated with HCC (p < 0.001). The treatment of chronic hepatitis C patients before they developed cirrhosis showed a higher efficacy than did the treatment of those who had already developed cirrhosis. Patients with SVR may still have a risk of HCC and need to be regularly monitored.
Endothelial Cell-derived Extracellular Vesicles Size-dependently Exert Procoagulant Activity Detected by Thromboelastometry
Authors: Holnthoner Wolfgang , Bonstingl Cornelia , Hromada Carina , Muehleder Severin , Zipperle Johannes , Stojkovic Stefan , Redl Heinz , Wojta Johann , Schöchl Herbert , Grillari Johannes , Weilner Sylvia , Schlimp Christoph J. 
Published: June 2017

AbstractEndothelial cells (ECs) are major modulators of hemostasis by expressing and releasing pro- and anticoagulant mediators into the circulation. Previous studies showed that cultured ECs release procoagulant mediators into cell culture supernatants as evidenced by the reduction of viscoelastic clotting time. This effect was reversed with an anti-tissue factor antibody. Here, we aimed to investigate whether tissue factor (TF) was released by endothelial-derived extracellular vesicles (EVs) and which portion of the released vesicles displays the most prominent procoagulant properties. After stimulation of ECs with tumor-necrosis factor-α (TNF-α) the supernatants of EC cultures were subjected to differential centrifugation steps to collect larger and smaller EVs which were then characterised by nanoparticle tracking analysis (NTA) and flow cytometry. Mixed with fresh human blood and analysed by thromboelastometry EVs exerted a significant procoagulant stimulus, which could be partly reversed by addition of an anti-TF antibody. Moreover, TF activity was confirmed in the centrifuged fractions. In summary, our results provide evidence of the procoagulant potential of smaller and larger endothelial-derived EV fractions detected by thromboelastometry. The observed effect is most likely due to the release of TF-bearing EVs of different dimensions, which are released upon TNF-α stimulation of endothelial cell cultures.
Arabidopsis Transporter ABCG37/PDR9 contributes primarily highly oxygenated Coumarins to Root Exudation
Authors: Ziegler Jörg , Schmidt Stephan , Strehmel Nadine , Scheel Dierk , Abel Steffen 
Published: June 2017

AbstractThe chemical composition of root exudates strongly impacts the interactions of plants with microorganisms in the rhizosphere and the efficiency of nutrient acquisition. Exudation of metabolites is in part mediated by ATP-binding cassette (ABC) transporters. In order to assess the contribution of individual ABC transporters to root exudation, we performed an LC-MS based non-targeted metabolite profiling of semi-polar metabolites accumulating in root exudates of Arabidopsis thaliana plants and mutants deficient in the expression of ABCG36 (PDR8/PEN3), ABCG37 (PDR9) or both transporters. Comparison of the metabolite profiles indicated distinct roles for each ABC transporter in root exudation. Thymidine exudation could be attributed to ABCG36 function, whereas coumarin exudation was strongly reduced only in ABCG37 deficient plants. However, coumarin exudation was compromised in abcg37 mutants only with respect to certain metabolites of this substance class. The specificity of ABCG37 for individual coumarins was further verified by a targeted LC-MS based coumarin profiling method. The response to iron deficiency, which is known to strongly induce coumarin exudation, was also investigated. In either treatment, the distribution of individual coumarins between roots and exudates in the investigated genotypes suggested the involvement of ABCG37 in the exudation specifically of highly oxygenated rather than monohydroxylated coumarins.
Gag-protease coevolution analyses define novel structural surfaces in the HIV-1 matrix and capsid involved in resistance to Protease Inhibitors
Authors: Codoñer Francisco M , Peña Ruth , Blanch-Lombarte Oscar , Jimenez-Moyano Esther , Pino Maria , Vollbrecht Thomas , Clotet Bonaventura , Martinez-Picado Javier , Draenert Rika , Prado Julia G. 
Published: June 2017

AbstractDespite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites. These residues were distributed in 23 Gag-protease groups of coevolution, with the viral matrix and the capsid represented in 87% and 52% of the groups. In addition, we uncovered the distribution of Gag correlated residues in specific protein surfaces of the inner face of the viral matrix and at the Cyclophilin A binding loop of the capsid. In summary, our findings suggest a tight interdependency between Gag structural proteins and the protease during the development of resistance of HIV-1 to PIs.
Theory of Inverse Edelstein Effect of The Surface States of A Topological Insulator
Authors: Geng H. , Luo W. , Deng W. Y. , Sheng L. , Shen R. , Xing D. Y. 
Published: June 2017

AbstractThe surface states of three-dimensional topological insulators possess the unique property of spin-momentum interlocking. This property gives rise to the interesting inverse Edelstein effect (IEE), in which an applied spin bias μ is converted to a measurable charge voltage difference V. We develop a semiclassical theory for the IEE of the surface states of Bi2Se3 thin films, which is applicable from the ballistic regime to diffusive regime. We find that the efficiency of the spin-charge conversion, defined as γ = V/μ, exhibits a universal dependence on the ratio between sample size and electron mean free path. The efficiency increases from γ = π/4 in the ballistic limit to γ = π in the diffusive limit, suggesting that sufficient strength of impurity scattering is favorable for the IEE.
Tamm plasmon modes on semi-infinite metallodielectric superlattices
Authors: Isić Goran , Vuković Slobodan , Jakšić Zoran , Belić Milivoj 
Published: June 2017

AbstractWe analyze the fundamental properties of optical waves referred to as Tamm plasmon modes (TPMs) which are tied to the interface of a semi-infinite two-phase metallodielectric superlattice with an arbitrary homogeneous capping medium. Such modes offer new ways of achieving high electromagnetic field localization and spontaneous emission enhancement in the vicinity of the interface in conjunction with absorption loss management, which is crucial for future applications. The homointerface, formed when the capping medium has the same permittivity as one of the superlattice constituents, is found to support a TPM whose dispersion overlaps the single-interface surface plasmon polariton (SPP) dispersion but which has a cut off at the topological transition point. In contrast, a heterointerface formed for an arbitrary capping medium, is found to support multiple TPMs whose origin can be traced by considering the interaction between a single-interface SPP and the homointerface TPM burried under the top layer of the superlattice. By carrying out a systematic comparison between TPMs and single-interface SPPs, we find that the deviations are most pronounced in the vicinity of the transition frequency for superlattices in which dielectric layers are thicker than metallic ones.
ADAMTS-7 is associated with a high-risk plaque phenotype in human atherosclerosis
Authors: Bengtsson Eva , Hultman Karin , Dunér Pontus , Asciutto Giuseppe , Almgren Peter , Orho-Melander Marju , Melander Olle , Nilsson Jan , Hultgårdh-Nilsson Anna , Gonçalves Isabel 
Published: June 2017

AbstractSeveral large-scale genome-wide association studies have identified single-nucleotide polymorphisms in the genomic region of A Disintegrin And Metalloproteinase with ThromboSpondin type 1 repeats (ADAMTS)-7 and associations to coronary artery disease. Experimental studies have provided evidence for a functional role of ADAMTS-7 in both injury-induced vascular neointima formation and development of atherosclerotic lesions. However, whether ADAMTS-7 is associated with a specific plaque phenotype in humans has not been investigated. Carotid plaques (n = 206) from patients with and without cerebrovascular symptoms were analyzed for expression of ADAMTS-7 by immunohistochemistry and correlated to components associated with plaque vulnerability. Plaques from symptomatic patients showed increased levels of ADAMTS-7 compared with lesions from asymptomatic patients. High levels of ADAMTS-7 correlated with high levels of CD68-staining and lipid content, but with low smooth muscle cell and collagen content, which together are characteristics of a vulnerable plaque phenotype. ADAMTS-7 levels above median were associated with increased risk for postoperative cardiovascular events. Our data show that ADAMTS-7 is associated with a vulnerable plaque phenotype in human carotid lesions. These data support previous observations of a potential proatherogenic role of ADAMTS-7.
A Unified Framework for Complex Networks with Degree Trichotomy Based on Markov Chains
Authors: Hui David Shui Wing , Chen Yi-Chao , Zhang Gong , Wu Weijie , Chen Guanrong , Lui John C. S. , Li Yingtao 
Published: June 2017

AbstractThis paper establishes a Markov chain model as a unified framework for describing the evolution processes in complex networks. The unique feature of the proposed model is its capability in addressing the formation mechanism that can reflect the “trichotomy” observed in degree distributions, based on which closed-form solutions can be derived. Important special cases of the proposed unified framework are those classical models, including Poisson, Exponential, Power-law distributed networks. Both simulation and experimental results demonstrate a good match of the proposed model with real datasets, showing its superiority over the classical models. Implications of the model to various applications including citation analysis, online social networks, and vehicular networks design, are also discussed in the paper.
Chromatin organization regulates viral egress dynamics
Authors: Aho Vesa , Myllys Markko , Ruokolainen Visa , Hakanen Satu , Mäntylä Elina , Virtanen Jori , Hukkanen Veijo , Kühn Thomas , Timonen Jussi , Mattila Keijo , Larabell Carolyn A. , Vihinen-Ranta Maija 
Published: June 2017

AbstractVarious types of DNA viruses are known to elicit the formation of a large nuclear viral replication compartment and marginalization of the cell chromatin. We used three-dimensional soft x-ray tomography, confocal and electron microscopy, combined with numerical modelling of capsid diffusion to analyse the molecular organization of chromatin in herpes simplex virus 1 infection and its effect on the transport of progeny viral capsids to the nuclear envelope. Our data showed that the formation of the viral replication compartment at late infection resulted in the enrichment of heterochromatin in the nuclear periphery accompanied by the compaction of chromatin. Random walk modelling of herpes simplex virus 1–sized particles in a three-dimensional soft x-ray tomography reconstruction of an infected cell nucleus demonstrated that the peripheral, compacted chromatin restricts viral capsid diffusion, but due to interchromatin channels capsids are able to reach the nuclear envelope, the site of their nuclear egress.
Tomographic Particle Image Velocimetry using Smartphones and Colored Shadows
Authors: Aguirre-Pablo Andres A. , Alarfaj Meshal K. , Li Er Qiang , Hernández-Sánchez J. F. , Thoroddsen Sigurdur T. 
Published: June 2017

AbstractWe demonstrate the viability of using four low-cost smartphone cameras to perform Tomographic PIV. We use colored shadows to imprint two or three different time-steps on the same image. The back-lighting is accomplished with three sets of differently-colored pulsed LEDs. Each set of Red, Green & Blue LEDs is shone on a diffuser screen facing each of the cameras. We thereby record the RGB-colored shadows of opaque suspended particles, rather than the conventionally used scattered light. We subsequently separate the RGB color channels, to represent the separate times, with preprocessing to minimize noise and cross-talk. We use commercially available Tomo-PIV software for the calibration, 3-D particle reconstruction and particle-field correlations, to obtain all three velocity components in a volume. Acceleration estimations can be done thanks to the triple pulse illumination. Our test flow is a vortex ring produced by forcing flow through a circular orifice, using a flexible membrane, which is driven by a pressurized air pulse. Our system is compared to a commercial stereoscopic PIV system for error estimations. We believe this proof of concept experiment will make this technique available for education, industry and scientists for a fraction of the hardware cost needed for traditional Tomo-PIV.
Spatio-Temporal Steering for Testing Nonclassical Correlations in Quantum Networks
Authors: Chen Shin-Liang , Lambert Neill , Li Che-Ming , Chen Guang-Yin , Chen Yueh-Nan , Miranowicz Adam , Nori Franco 
Published: June 2017

AbstractWe introduce the concept of spatio-temporal steering (STS), which reduces, in special cases, to Einstein-Podolsky-Rosen steering and the recently-introduced temporal steering. We describe two measures of this effect referred to as the STS weight and robustness. We suggest that these STS measures enable a new way to assess nonclassical correlations in an open quantum network, such as quantum transport through nano-structures or excitation transfer in a complex biological system. As one of our examples, we apply STS to check nonclassical correlations among sites in a photosynthetic pigment-protein complex in the Fenna-Matthews-Olson model.